Search

Yellow fever (YF) is a viral disease that affects both humans and non-human primates (NHPs). Neotropical monkeys are more severely stricken by YF and the impact of the disease can be devastating to the endangered golden-headed lion tamarins (GHLTs, Leontopithecus chrysomelas). Susceptible GHLTs were immunized with the commercial Brazilian YF 17DD live attenuated vaccine or two other experimental non-replicating YF vaccines: a purified whole-virus, b-propiolactone-inactivated vaccine and a plant-derived recombinant subunit vaccine. Safety, immunogenicity and viremia and RNAemia blockade were characterized. No YF clinical manifestations were observed in any of the GHLTs that received the attenuated virus, either as a vaccine or as the homologous vaccination with the live attenuated vaccine used as the challenge virus. All three concentrations of the attenuated vaccine induced neutralizing antibodies and only one in 16 animals had detectable viremia and RNAemia after challenge. The inactivated vaccine elicited neutralizing antibodies preventing post-challenge viremia and RNAemia in five out of six animals. The plant-based vaccine induced neutralizing antibodies in five out of six animals and prevented viremia and RNAemia in three out of six against challenge. The safety profile and the immunogenicity of the YF attenuated vaccine were demonstrated in GHLTs with a blocking effectiveness over 90 %, where blockade can be defined as the capacity to prevent viremia and RNAemia after homologous vaccination with the live attenuated vaccine. The use of the inactivated vaccine in this species served as a preliminary pre-clinical study for this approach and after administration in three-dose regimen demonstrated a blocking profile of 83 %. Using a two-dose regimen, the plant-based vaccine was able to block viremia and RNAemia in 50 % of the animals. The present study can endorse the use of attenuated or non-replicating yellow fever vaccines in New World primates threatened by the recent disease outbreaks in Brazil., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Coronaviruses have large, positive-sense single-stranded RNA genomes that challenge conventional strategies for mutagenesis. Yeast genetics has been used to manipulate large viral genomes, including those of herpesviruses and coronaviruses. This method, known as transformation-associated recombination (TAR), involves assembling complete viral genomes from dsDNA copies of viral genome fragments via homologous recombination in Saccharomyces cerevisiae . Here, we report our development of a TAR assembly and mutagenesis system for the endemic, seasonal human coronavirus (HCoV) strain OC43. HCoV-OC43 generally causes mild respiratory symptoms and is classified as a biosafety level 2 agent, making it useful for studying fundamental aspects of coronavirus biology and for comparative studies of more highly pathogenic betacoronaviruses. Following cDNA synthesis from HCoV-OC43 viral RNA, we generated five plasmids encompassing ~7.2 kb portions of the ORF1ab gene, the NS2 to M segment, or the N gene and structured to facilitate reporter gene insertions in the M -to- N intergenic region. Using these plasmids, we completed independent assemblies of yeast centromeric plasmids encoding ORF1ab , NS2a to N , as well as full-length HCoV-OC43 plasmids. A wild-type virus (OC43 YA ), as well as mClover3-H2B (OC43-mClo YA ), mRuby3-H2B (OC43-mRuby YA ), and mCardinal (OC43-mCard YA ) reporter viruses, were rescued. The OC43-mClo YA reporter virus replicated comparably to an OC43 reference strain and produced the mClover3-H2B protein from a novel subgenomic RNA through insertion of an eighth body transcription regulatory sequence, preventing the need to delete or mutate viral genes. This updated HCoV-OC43 reverse genetics system will contribute to a better understanding of betacoronavirus host-pathogen interactions and can accelerate studies of novel antivirals., Importance: Coronaviruses are ubiquitous pathogens that infect humans resulting in both mild and severe respiratory infections. Human coronavirus strain OC43 (HCoV-OC43) is one of many viruses responsible for common colds and is a useful model of more severe coronavirus infections. In this study, we describe an updated HCoV-OC43 mutagenesis system that uses yeast to capture six DNA fragments of the viral RNA genome and assemble them into full-length genomes in yeast/bacterial plasmids. The design of this system allowed for the rapid assembly and rescue of functional HCoV-OC43 viruses, including fluorescent reporter viruses with expanded genetic capacity. This updated reverse genetics system will enhance our ability to monitor viral replication, through building new reporter viruses, while also enhancing the study of betacoronavirus biology through the generation of mutant HCoV-OC43 viruses., Competing Interests: The authors declare no conflict of interest.

Nile tilapia (Oreochromis niloticus) is an important food source worldwide and plays a significant role in Mexico's aquaculture industry. However, it faces increasing challenges from disease outbreaks threatening this sector. From recent research and epidemiological data, this review examines the diseases impacting tilapia aquaculture in Mexico. It analyses bacterial, parasitic, viral, and fungal infections, providing insights into their clinical signs, etiological agents, treatment strategies, and geographical distribution across various Mexican states. The study highlights four major parasitic infections: Cichlidogyrus Infection, Gyrodactyliasis, Neobenedeniosis and Trichodiniasis. Six prominent bacterial infections are discussed, including motile Aeromonas septicaemia (MAS), Streptococcosis, Staphylococcosis, Francisellosis, Edwardsiellosis and Mycobacteriosis. It addresses Saprolegniasis, a fungal infection affecting tilapia eggs and the overall health of hatcheries. Additionally, it highlights technical information on the Tilapia Lake Virus (TiLV), which poses a significant viral threat. This analysis examines the three-level diagnostic system for infectious diseases in aquaculture outlined by the FAO, emphasising its application in tilapia aquaculture in Mexico. The system includes (i) implementing prevention strategies, biosecurity protocols and good management practices (Level I); (ii) conducting laboratory-based diagnostic tests (Level II); and (iii) utilising advanced molecular techniques for early disease detection (Level III). By adopting these measures, the aquaculture sector can effectively mitigate disease outbreaks, thereby promoting the sustainable growth and long-term success of tilapia farming in Mexico., (© 2025 John Wiley & Sons Ltd.)

Emerging evidence indicates that gingival-resident helper CD4 + T cells are major drivers of periodontal inflammation in response to commensal and pathogenic oral microorganisms. Whether tissue-resident memory CD8 + T cells (T RM ), which principally safeguard against viruses and cancer but also drive certain autoimmune and inflammatory conditions, impact periodontitis progression and severity remain unknown. We asked whether local reactivation of oral CD8 + T RM of a defined antigen specificity could exacerbate ligature-induced periodontitis (LIP), a well-established model of periodontal disease in mice. Topical application of virus-mimicking peptides to the oral mucosa concurrent with LIP 1) intensified alveolar bone loss, 2) amplified gingival and cervical lymph node inflammation, and 3) stimulated gingival transcriptional changes in genes related to innate immune sensing and cell-mediated cytotoxicity. Therapeutic depletion of CD103-expressing oral CD8 + T RM in advance of LIP prevented exacerbation of disease. These observations provide evidence that oral CD103 + CD8 + T RM have the potential to participate in gingival inflammation, alveolar bone loss, and periodontitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

NONEXPRESSER OF PATHOGENESIS-RELATED GENES 1 (NPR1), the receptor for salicylic acid (SA), plays a central role in the SA-mediated basal antiviral responses. Recent studies have shown that two different plant RNA viruses encode proteins that suppress such antiviral responses by inhibiting its SUMOylation and inducing its degradation, respectively. However, it is unclear whether targeting NPR1 is a general phenomenon in viruses and whether viruses have novel strategies to inhibit NPR1. In the present study, we report that two different positive-sense single-stranded RNA (+ssRNA) viruses, namely, alfalfa mosaic virus (AMV) and potato virus X (PVX); one negative-sense single-stranded RNA (-ssRNA) virus (calla lily chlorotic spot virus, CCSV); and one single-stranded DNA virus (beet severe curly-top virus, BSCTV) that also encode one or more proteins that interact with NPR1. In addition, we found that the AMV-encoded coat protein (CP) can induce NPR1 degradation by recruiting S-phase kinase-associated protein 1 (Skp1), a key component of the Skp1/cullin1/F-box (SCF) E3 ligase. In contrast, the BSCTV-encoded V2 protein inhibits NPR1 function, probably by affecting its nucleocytoplasmic distribution via the nuclear export factor ALY. Taken together, these data suggest that NPR1 is one of the central hubs in the molecular arms race between plants and viruses and that different viruses have independently evolved different strategies to target NPR1 and disrupt its function., (© 2025 The Author(s). Journal of Integrative Plant Biology published by John Wiley & Sons Australia, Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.)

Infectious diseases have become significant events that threaten global public health and economic development. Since the 20th century, multiple outbreaks of infectious diseases have gradually deepened humanity's understanding of viral infections, prevention and treatment. Organoids possess a high degree of similarity to human physiological states and have strong self-organising capabilities. Research on infectious diseases based on organoids offers significant advantages in terms of availability, editability and diversity. In this perspective, we briefly introduce the development of organoids, focusing on historically significant infectious diseases that have caused fatal harm to human health, such as HIV, ZIKV, SARS-CoV-2 and MPXV. We further summarise relevant research on the pathogenic mechanisms of these viruses based on organoid models, host reactivity, and therapeutic strategies. Finally, we list the latest research techniques combined with organoid models, discuss the challenges faced in the development of organoids and look forward to the future prospects of organoids in vaccine and drug development., (© 2025 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Dengue, a formidable life-threatening malady, currently exerts a profound impact upon the Western Pacific and Southeast-Asian developing and underdeveloped nations. The intricacies inherent in addressing dengue are manifold, requiring a concerted effort not only towards vector control but also the implementation of efficacious host treatments to forestall the progression of the disease into severe manifestations, such as hemorrhage and shock. The only vaccine available for dengue in the market is DENGVAXIA, with several other vaccine candidates which are currently in the clinical developmental stages. However, DENGVAXIA, owing to incidences of adverse events in among children, was withdrawn in Philippines. This warrants the development of new safer vaccine candidates. The existent control strategies, regrettably, demonstrate inadequacy in effectively mitigating the rampant dissemination of this ailment. Moreover, the diagnostic and therapeutic modalities exhibit potential for refinement, specifically through precision diagnostics and tailored therapeutic interventions, to enhance the precision and efficacy of dengue management. This comprehensive review endeavors to provide an in-depth elucidation of the utilization of nanotechnology-based approaches synergistically integrated with conventional methodologies in the overarching domains of dengue control, diagnosis, and treatment., Competing Interests: Declarations. Conflict of interest: No conflict of interest was reported by the authors related to this article., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The food safety and medical health issues caused by pathogen are particularly prominent. The development of biosensing technologies is urgent to ensure pathogenic biosafety. Argonaute system, as a promising and cutting-edged next-generation nucleic acid test technology, has the potential to address the challenges faced by CRISPR/Cas system. In this review, we focused on the current state-of-art Argonaute-powered biosensing for pathogenic biosafety. First, we introduced current methods for nucleic acid testing and programmable nucleases, followed by the working principle of Argonaute system (PfAgo, TtAgo, CbAgo, etc). Then Argonaute-medicated nucleic acid biosensing was highlighted through amplification and amplification-free manners. In addition, we summarized the application of Argonaute tools in detecting bacteria, virus, mycoplasma, etc. Finally, we pointed out the challenges and perspectives. Current pathogen methods demonstrate low sensitivity and specificity, as well as lack capabilities for multiple and point-of-care testing. Recent studies have shown that Argonaute-powered biosensing is an innovative and rapidly growing technology that could significantly enhance detection capabilities for pathogen-related issues, addressing the limitations of current methods. The application of Argonaute-powered biosensing is both promising and desirable due to the potential to offer "customized" and streamlined detection in the field of pathogenic biosafety monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Aims: miRNAs, small non-coding RNAs, play key roles in gene regulation, cell differentiation and tissue development. They influence viral infection outcomes by directly interacting with viral genomes or modifying the host microenvironment. This study demonstrates miRNAs' ability to selectively suppress transcriptionally active erythroparvovirus, highlighting their potential in antiviral therapies., Methods and Results: Seventy-five endomyocardial biopsy (EMB) specimens from patients with unexplained heart failure were analysed. The samples included 19 with dilated cardiomyopathy and inflammation (DCMi), 12 with dilated cardiomyopathy (DCM), 25 with inflammation and active erythroparvovirus infection, 13 with active erythroparvovirus infection only and 6 from undiagnosed patients as controls. miRNA expression was measured using TaqMan assays. miR-98, miR-222, miR-106b and miR-197 were significantly upregulated in patients with transcriptionally active erythroparvovirus infection, independent of inflammation (P < 0.005). These miRNAs differentiated these patients from all other groups with over 90% specificity., Conclusions: These specific miRNAs offer a novel diagnostic tool for active erythroparvovirus infections and hold promise as therapeutic targets, providing safer alternatives to traditional antiviral treatments., (© 2025 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Papillomas, many of which are virally induced, are common proliferative cutaneous and mucocutaneous lesions in multiple species, exhibiting characteristic histologic cytopathic changes that distinguish them from nonviral squamous papillomas. A single case report of a novel papillomavirus, Ursus maritimus papillomavirus-type 1, in a polar bear has been reported without investigation into any association between this virus and papilloma formation. We identified papillomas in 3 polar bears. All 3 cases had pedunculated masses consistent with papillomas (i.e., proliferative epithelium forming papillary projections on a fibrovascular stalk); case 1 also exhibited koilocytosis (cytopathic change), consistent with a viral papilloma. Polymerase chain reaction (PCR) using primers that can amplify a diversity of papillomaviruses followed by amplicon sequencing yielded a novel papillomavirus sequence in case 1, which shared <70% nucleotide identity to any known papillomavirus type, indicative of a putatively novel papillomavirus. In situ hybridization (ISH) of case 1 demonstrated viral nucleic acid within proliferative cells and not within the adjacent normal skin, suggesting the virus was the causative agent of this papilloma. The squamous papillomas in cases 2 and 3 were negative for papillomavirus by both PCR and ISH. These findings support our hypothesis that cytopathic effect is associated with the presence of papillomavirus in polar bears, while the lack of histologic cytopathic change may predict nonviral pathogenesis. Further sequencing of the putatively novel viral genome will benefit research and conservation efforts of polar bears., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cytoplasmic viruses interact intricately with the nuclear pore complex and nuclear import/export machineries, affecting nuclear-cytoplasmic trafficking. This can lead to the selective accumulation of nuclear RNA-binding proteins (RBPs) in the cytoplasm. Pioneering research has shown that relocated RBPs serve as an intrinsic defense mechanism against viruses, which involves RNA export, splicing, and nucleolar factors. For instance, the U2 small nuclear ribonucleoprotein (snRNP) relocates to the cytoplasm in infected cells and uses U2 snRNA to interact with viral genomes, repressing viral replication and gene expression. Here, we describe these emerging host-virus interactions and discuss the remaining questions to elucidate their antiviral mechanisms., (© 2025 Castello and Kamel; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Background: Contacts between people and free-ranging animals have a potential to cause viral disease epidemics when novel viruses are exchanged. The Netherlands has approximately 18 native bat species, of which some generally use buildings for roosting, and has a dense human population. Frequent indirect and direct contacts between bats and humans could thus be expected, however, this has hardly been studied., Methods: To study human-bat contacts, people living in the Netherlands were questioned about the type and frequency of their bat contacts, their bat knowledge and perception of bats. For analyses respondents were grouped into (1) general population, (2) bat contact risk group, and (3) people that live in a house with a roost site for a Common Pipistrelle Bat maternity group. Associations between human-bat contacts and other variables were tested by an ordinal logistic regression model., Results: We show that 85% (226/265) of group 1 reported no contacts, while 11% (28/265) reported indirect, and 4% (11/265) direct contacts with live bats, dead bats or bat products as their closest type of contacts. These contacts occurred mostly less than yearly. Somewhat similarly, the majority, 69% (9/13) of group 3 reported no contacts, and 15% (2/13) reported indirect contacts and 15% (2/13) reported direct contacts. These occurred monthly to less than yearly. In contrast, a minority, 5% (11/227) in group 2 reported no contacts, while 37% (85/227) reported direct bat contacts, mostly yearly, and 38% (86/227) reported bat-related injury, mostly less than yearly, as their closest type of contact. Overall, an increase in knowledge on bats and bat-related diseases was correlated with closer bat contacts., Conclusions: We conclude that even though bats live close to people in the Netherlands, direct contacts between bats, or bat products, and humans are rare in people from the general population, while being common in people involved in bat-related work. Mitigation of human-bat contacts will be most efficient when targeted to specific groups that are likely to have contacts with bats., Competing Interests: Declarations. Ethics approval and consent to participate: All participants included in this study were informed about the purpose of the study, and have approved their data to be used. The project, questionnaire and informed consent were evaluated and approved by the Medical Ethical Committee of Erasmus Medical Centre (MEC-2018-102; NL64612.078. 18, v4). Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Eutrophication of lake and reservoir caused by cyanobacterial harmful algal blooms (cyanoHABs) become a global ecological problem because of massive destruction of ecosystems, which have attracted attentions widely. In addition to the production of cyanotoxins by certain bloom-forming species, there may also be direct or indirect interactions between cyanobacteria blooms and various pollutants in lakes or reservoirs. Based on bibliometrics, 19110 papers in Web of Science (WOS) and 2998 papers in the China National Knowledge Infrastructure (CNKI) on eutrophication and cyanobacterial blooms in lakes and reservoirs were analyzed, which showed that research on this topic has been ongoing for nearly 80 years with a gradual increase in its popularity. The research on the coupling process of cyanobacterial blooms with five typical pollutants, including microcystins (MCs), heavy metals, viruses, antibiotics and antibiotic resistance genes (ARGs), indicate that the coupling process between cyanobacteria blooms and certain pollutants is indeed generated through direct or indirect interactions by adsorption, changing the physical and chemical conditions of water environment, and changing the structure of microbial community. For instance, the production, toxicity would be likely enhanced by cyanobacteria blooms directly. And the microorganisms may play a significant role in the interaction between cyanobacteria blooms and ARGs. Generally, the risk of some typical pollutants would be likely enhanced or decreased directly or indirectly by these processes. It is recommended that further attention be paid to the interrelationships between the process of cyanobacterial bloom and typical pollutants' migration and transformation, to provide the scientific basis for the risk assessment and thus multi-objective synergistic control and management of nutrients and typical pollutants in eutrophic lakes or reservoirs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Over the past decade, the continuous and rapid advances in bioinformatics have led to an increasingly common use of molecular sequence comparison for phylogenetic analysis. However, the use of multi-software and cross-platform strategies has increased the complexity of phylogenetic tree estimation. Therefore, the development and application of streamlined phylogenetic analysis tools are growing in significance in the field of biology. Particularly for genomes with relatively short sequences, there is a lack of simple and integrative tools for phylogenetic analysis., Results: In this study, we present CamlTree (Concatenated alignments maximum-likelihood tree), a user-friendly desktop software designed to simplify phylogenetic analysis for viral and mitochondrial genomes, ultimately facilitating related research. CamlTree provides a workflow including gene concatenation (or coalescence), sequence alignment, alignment optimization, and the estimation of phylogenetic trees using both maximum-likelihood (ML) and Bayesian inference (BI) methods. CamlTree was written in TypeScript and developed using the Electron framework. It offers a primarily user-friendly interface based on the React framework., Conclusions: CamlTree software has been released for the Windows OS. It integrates several popular analysis tools to optimize and simplify the process of estimating polygenic phylogenetic trees. The establishment of software can assist researchers in reducing their workload and enhancing data processing efficiency, enabling them to expedite their research progress. The software, along with a detailed user manual, is available at https://github.com/BioCrossCoder/camltree ., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

This review provides an overview of electron beam (eBeam) technology and its applications across a wide variety of disciplines. More importantly, it discusses this technology's advantages and its benefits in developing inactivated vaccines. eBeam technology is currently being used all around the world for a variety of industrial applications, extending from food pasteurization to the cross-linking of polymers in the wire and cable industries. It is a successful emerging alternative for developing vaccines against bacterial, protozoan, and viral pathogens. This review includes a descriptive account of the mechanism of action of eBeam and how this technology achieves the complete inactivation of pathogens while retaining the integrity of their surface epitopes. This unique advantage is crucial for the production of efficacious vaccines. This review provides a detailed account of the usage of eBeam technology for developing vaccines to protect a multitude of hosts against a wide range of pathogens. eBeam-inactivated vaccines are advantageous over live vaccines, RNA/subunit vaccines, and chemically inactivated vaccines mainly due to the complete inactivation of pathogens, and the presence of intact, highly antigenic epitopes. To conclude, this article descriptively highlights eBeam technology's advantages over other means of vaccine development.

By the end of the nineties, new immunomodulatory options impacting on the determinants of many immune-mediated diseases became available. These drugs were also called biologicals. Their use was associated with a significant improvement in the management of the patients and on their clinical evolution over time. On the other hand, their use was found to be also associated with an over-risk of infectious complications, in particular of viral origin, even though the savings of other at-risk treatments (e.g. corticosteroids or cyclophosphamide) allowed by these new therapies could have contributed to reduce it. These viral infections may be linked to an increased susceptibility to new infections because of impaired immunity and/or lower responsiveness to vaccination, to a higher risk of reactivation of latent infections, and to a higher severity than observed in the general population. Viruses mostly involved are respiratory (influenza, RSV, and SARS-CoV2), Varicella-Zoster, hepatitis B, or JC viruses, in particular. The viral risk depends not only on the type of biologicals, but also on the underlying disease, the associated comorbidities, the associated treatments, the epidemiological environment, and the individual and collective immunity. At an individual level, prevention and management of the infectious risk are of utmost importance in the global management of patients on biologicals., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Evidence suggests that bats are important hosts of filoviruses, yet the specific species involved remain largely unidentified. Niemann-Pick C1 (NPC1) is an essential entry receptor, with amino acid variations influencing viral susceptibility and species-specific tropism. Herein, we conducted combinatorial binding studies with seven filovirus glycoproteins (GPs) and NPC1 orthologs from 81 bat species. We found that GP-NPC1 binding correlated poorly with phylogeny. By integrating binding assays with machine learning, we identified genetic factors influencing virus-receptor-binding and predicted GP-NPC1-binding avidity for additional filoviruses and bats. Moreover, combining receptor-binding avidities with bat geographic distribution and the locations of previous Ebola outbreaks allowed us to rank bats by their potential as Ebola virus hosts. This study represents a comprehensive investigation of filovirus-receptor binding in bats (1,484 GP-NPC1 pairs, 11 filoviruses, and 135 bats) and describes a multidisciplinary approach to predict susceptible species and guide filovirus host surveillance., Competing Interests: Declaration of interests D.L. is employed by Schrodinger Inc. and holds company stocks. K.C. holds shares in Integrum Scientific, LLC, and Eitr Biologics Inc., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Acute bee paralysis virus (ABPV) is a notable pathogen frequently detected in managed honeybee (Apis mellifera) colonies. Although infections are often covert, they can lead to severe outcomes in the presence of Varroa destructor infestations. This study aims to evaluate the prevalence of ABPV and its correlation with a range of biotic and abiotic stressors in managed beehives located in the Central Anatolia and Mediterranean Regions of Türkiye during the spring-summer and autumn seasons of 2021. ABPV was identified in 38.6% of the samples (27/70) using real-time RT-PCR. The high prevalence observed was linked to Varroa destructor infestations, elevated temperatures and dry climatic conditions, migratory beekeeping practices, and disruptions in colony management during the COVID-19 pandemic. Phylogenetic relationships among ABPV strains were elucidated through partial sequencing of the capsid and RNA-dependent RNA polymerase protein coding genes, employing maximum likelihood tree construction with the Tamura 3-parameter model. Turkish ABPV strains clustered into a distinct subclade, sharing 98.4-99% nucleotide identity with European strains, indicative of a monophyletic origin and geographic segregation at the regional or continental level. These findings highlight the necessity for robust surveillance and research programs to monitor ABPV prevalence and mitigate its detrimental effects on colony health and productivity. Additionally, the phylogenetic insights provided by this study enhance our understanding of the geographic distribution and evolutionary dynamics of ABPV strains, offering critical information for future molecular epidemiological research and apicultural management strategies., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflicts of interest. Ethical approval: This study was approved by the Selçuk University Animal Experiments Local Ethics Committee (Approval no: SÜVDAMEK, 2020-117 on 28/12/2020)., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Binding to cellular receptors initiates viral replication and dictates sites in the host infected by the virus. As illustrated by mammalian orthoreovirus (reovirus), viruses can bind several types of receptors using distinct capsid components to facilitate the viral entry steps of attachment, internalization, and disassembly. The outer of the two concentric capsids of reovirus virions is formed by four viral proteins, three of which bind receptors. These capsid-receptor interactions mediate stepwise entry of reovirus, dictate viral tropism in infected animals, and expand the viral host range. Engagement of independent receptors by different capsid proteins is a property of many pathogenic viruses and illustrates common themes of receptor use in viral entry and disease.

Evidence from both field and experimental studies suggests that recombination is a common feature in the evolution of foot-and-mouth disease virus (FMDV). Recent studies have demonstrated that heterologous superinfection of cattle persistently infected with FMDV leads to rapid generation of inter-serotypic recombinant viruses in the upper respiratory tract mucosa. The current study demonstrates that the order of exposure to FMDV strains A24 Cruzeiro and O1 Manisa substantially influenced the patterns of mosaicism of resultant recombinants. FMDV recombinants were isolated from oropharyngeal fluid samples from 7 of 12 cattle following heterologous superinfection at 21 days post-initial infection. There was no apparent competitive advantage of either parental virus. However, recombinant viruses recovered from six of seven animals had gained, or regained through multiple recombination events, the capsid-coding sequence of FMDV O1 Manisa despite the presence of high titers of neutralizing antibodies against that virus. Additionally, a sub-genomic region of high amino acid diversity, spanning the 3' portion of 3A through 3B, was derived from FMDV A24 in most of the recovered recombinants. Despite the frequent recovery of FMDV recombinants from the upper respiratory tract of superinfected animals, there was no detection of recombinant viruses in blood or lesions in the subset of animals that developed clinical foot-and-mouth disease during superinfection. Overall, these findings confirm the high frequency at which FMDV recombination occurs when persistently infected carrier cattle are exposed to a heterologous virus and reaffirm that superinfection of carriers should be considered as a source of FMDV genetic diversity in endemic regions.IMPORTANCEFoot-and-mouth disease virus (FMDV) is a pathogen of domestic livestock with profound global socioeconomic impacts. FMDV causes a subclinical persistent infection in ruminant hosts, such as cattle, during which the animals may become sequentially infected by heterologous variants of the virus. Our previous works have demonstrated that such superinfections frequently lead to emergence of novel recombinant virus variants in the upper respiratory tracts of infected animals. This current investigation demonstrates that the order in which the animals are exposed to two different viruses substantially influences the structure of resultant recombinant genomes and confirms the frequency at which FMDV recombination occurs following heterologous superinfection of persistently infected FMDV carriers.

Viruses are ubiquitous, and their potential impacts on biogeochemical cycles in soil have largely been inferred from correlation evidence and virome studies. Manure has been demonstrated to affect nitrogen cycle by altering soil nutrients and microbial communities. However, the direct impacts of viruses derived from manure on microbial community, nitrification, and denitrification remained exclusive. In this study, concentrated viral extracts obtained from manure were added into an agricultural soil in varying dosages: a one-time addition of 10-fold viruses or a weekly addition of 1-fold viruses for ten weeks. The results showed that both viral extracts and manure significantly changed the microbial community compositions and structures. The effect of manure on microbial diversity was concentration-dependent, differing from the viral impact on microbial diversity in soil. Deterministic processes predominated in the assembly of microbial communities in both viral and manure treatments, with an increased contribution of deterministic processes observed after these treatments. Additionally, a high concentration (10-fold) of viruses enhanced N 2 O production and reduction in soil. In the control treatment, N 2 O production was driven by bacterial denitrification, fungal denitrification, and chemo-denitrification. However, bacteria became the dominant driver of N 2 O production in both virus and manure treatments. Overall, experimental evidence for viral impacts on the composition and assembly of microbial community, as well as on nitrification and denitrification processes, was provided through a 70-day microcosm experiment. These findings highlight the importance of viruses in regulating the distribution and functioning of microbes in terrestrial ecosystems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Background: Viral vaccines have been proven significant in protecting us against viral diseases such as COVID-19. To better understand and design viral vaccines, it is critical to systematically collect, annotate, and analyse various viral vaccines and identify enriched patterns from these viral vaccines., Methods: We systematically collected experimentally verified viral vaccines from the literature, manually annotated, and stored the information in the VIOLIN vaccine database. The annotated information included basic vaccine names, pathogens and diseases, vaccine components, vaccine formulations, and their induced host responses. Enriched patterns were identified from our systematical analysis of the viral vaccines and vaccine antigens., Results: A total of 2,847 viral vaccines against 95 viral species (including 72 RNA viral species and 23 DNA viral species) were collected, manually annotated, and stored in the VIOLIN vaccine database. These viral vaccines used 542 vaccine antigens. A taxonomical analysis found various DNA and RNA viruses covered by the viral vaccines. These vaccines target different viral life cycle stages (e.g., viral entry, assembly, exit, and immune evasion) as identified in top ranked human, animal vaccines, and HPV vaccines. The vaccine antigen proteins also show up in different virion locations in viruses such as HRSV vaccines. Both structural and non-structural viral proteins have been used for viral vaccine development. Protective vaccine antigens tend to have a protegenicity score of >85% based on the Vaxign-ML calculation, which measures predicted suitability for vaccine use. While predicted adhesins still have significantly higher chances of being protective antigens, only 21.42% of protective viral vaccine antigens were predicted to be adhesins. Furthermore, our Gene Ontology (GO) enrichment analysis using a customized Fisher's exact test identified many enriched patterns such as viral entry into the host cell, DNA/RNA/ATP/ion binding, and suppression of host type 1 interferon-mediated signaling pathway. The viral vaccines and their associated entities and relations are ontologically modeled and represented in the Vaccine Ontology (VO). A VIOLIN web interface was developed to support user friendly queries of viral vaccines., Discussion: Viral vaccines were systematically collected and annotated in the VIOLIN vaccine knowledgebase, and the analysis of these viral vaccines identified many insightful patterns., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Huffman, Gautam, Gandhi, Du, Austin, Roan, Zheng and He.)

COVID-19 antibody detection is dependent on highly specialized, time-consuming techniques, such as PCR separation, DNA amplification, and other methods such as spectrophotometric absorption. For these reasons, specialized technical training is necessary because individual diagnostic treatment is difficult. We have attempted to perform rapid sensing with a detection time of only 30 s. Additionally, we used a wearable multi-layer graphene oxide nanocolloid synthetic skin tattoo probe assay for influenza and COVID-19 virus detection with an electrochemical antigen-antibody redox ionic titration circuit. Cyclic voltametric-2 V~2.0 V potential windows were used. The diagnostic detection limit was determined using stripping anodic and cathodic amplifiers, and the working probe was fabricated with a graphene molecule structure with a virus antigen-immobilized amplifier. With redox potential strength obtained within -1.0 V~-1.3 V ionic activity, anodic and cathodic current linearly increased in the phosphate-buffered saline 5 mL electrolyte. The results indicate that instant detection was enabled via individual and wearable tattoo sensors.

Reef fishes exhibit enormous biodiversity within a highly interactive ecosystem. Relatively little is known about the diversity and evolution of microbial species associated with reef fish, even though this may provide valuable insights into the factors that shape microbial communities. Through metatranscriptomic sequencing we characterised the viruses, bacteria, and single-celled eukaryotes from 126 reef fish species inhabiting Lizard Island and Orpheus Island on the Great Barrier Reef, Australia. We assessed whether microbial communities differed between islands that are separated by 450 kilometres, and to what extent fish viruses emerge in new hosts. Despite strong ecological interactions within the species-rich reef environment, and the presence of the same families of viruses on both islands, there was minimal evidence for the presence of individual viruses shared among fish species, reflecting low levels of cross-species transmission. Among bacteria, we identified the opportunistic bacterial pathogen Photobacterium damselae in apparently healthy cardinalfish species from both islands, indicating that these fish species are natural reservoirs. These data suggest that reef fishes have microbial-host associations that arose prior to the formation of the Great Barrier Reef, likely leading to strong host barriers to cross-species transmission and hence infectious disease emergence., (© The Author(s) 2025. Published by Oxford University Press on behalf of FEMS.)

Cockroaches serve as mechanical vectors for medically important pathogens, and their presence in hospitals is a common occurrence. This review summarizes the pathogens carried by cockroaches collected in hospitals around the world during the period 2000-2024 and focuses on their antibiotic resistance mechanisms and potential impact on the public health system. The conventional techniques are most used to identify microorganisms and determine antibiotic resistance, but there are few studies that use molecular techniques for bacterial identification and resistance mechanism detection. The species that appear most frequently in the selected articles were Escherichia coli (22 articles) and Pseudomonas aeruginosa (11 articles). Regarding antibiotic resistance, this review describes 79.0% (34/43) of the studies analyzed. E. coli and P. aeruginosa bacteria were found to be resistant to antibiotics in 51.2% and 25.6% of articles, respectively. The identification of pathogens carried by cockroaches collected in hospitals suggests a potential risk of these insects in the transmission of healthcare-associated infections, mainly in developing countries, where this issue is most alarming. The collected data suggest that integrated approaches to cockroach control and infestation management should be put in place based on scientific evidence.

Ovarian cancer (OC) remains the most lethal gynecologic malignancy with limited effective treatment options. Oncolytic viruses (OVs) have emerged as a promising therapeutic approach for cancer treatment, capable of selectively infecting and lysing cancer cells while stimulating anti-tumor immune responses. Preclinical studies have demonstrated significant tumor regression and prolonged survival in OC models using various OVs, such as herpes simplex. Early-phase clinical trials have shown a favorable safety profile, though the impact on patient survival has been modest. Current research focuses on combining OVs with other treatments like immune checkpoint inhibitors to enhance their efficacy. We provide a comprehensive overview of the current understanding and future directions for utilizing OVs in the management of OC.

Acute respiratory infections (ARIs) caused by viruses such as SARS-CoV-2, influenza viruses, and respiratory syncytial virus (RSV), pose significant global health challenges, particularly for the elderly and immunocompromised individuals. Substantial evidence indicates that acute viral infections can manipulate the host's epigenome through mechanisms like DNA methylation and histone modifications as part of the immune response. These epigenetic alterations can persist beyond the acute phase, influencing long-term immunity and susceptibility to subsequent infections. Post-infection modulation of the host epigenome may help distinguish infected from uninfected individuals and predict disease severity. Understanding these interactions is crucial for developing effective treatments and preventive strategies for viral ARIs. This review highlights the critical role of epigenetic modifications following viral ARIs in regulating the host's innate immune defense mechanisms. We discuss the implications of these modifications for diagnosing, preventing, and treating viral infections, contributing to the advancement of precision medicine. Recent studies have identified specific epigenetic changes, such as hypermethylation of interferon-stimulated genes in severe COVID-19 cases, which could serve as biomarkers for early detection and disease progression. Additionally, epigenetic therapies, including inhibitors of DNA methyltransferases and histone deacetylases, show promise in modulating the immune response and improving patient outcomes. Overall, this review provides valuable insights into the epigenetic landscape of viral ARIs, extending beyond traditional genetic perspectives. These insights are essential for advancing diagnostic techniques and developing innovative treatments to address the growing threat of emerging viruses causing ARIs globally.

Phytochemicals are typically natural bioactive compounds or metabolites produced by plants. Phytochemical-loaded nanocarrier systems, designed to overcome bioavailability limitations and enhance therapeutic effects, have garnered significant attention in recent years. The coronavirus disease 2019 (COVID-19) pandemic has intensified interest in the therapeutic application of phytochemicals to combat viral infections. This review explores nanoparticle-based treatment strategies incorporating phytochemicals for antiviral application, highlighting their demonstrated antiviral mechanisms. It specifically examines the antiviral activities of phytochemical-loaded nanosystems against (i) influenza virus (IAV), respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); (ii) mosquito-borne viruses [dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV)]; and (iii) sexually transmitted/blood borne viruses [e.g. herpes simplex virus (HSV), human papillomavirus (HPV), and human immunodeficiency virus (HIV)]. Furthermore, this review highlights the emerging role of these nanosystems in photodynamic therapy (PDT)-mediated attenuation of viral proliferation, and offers a perspective on the future directions of research in this promising area of multimodal therapeutic approach.

The study of invertebrate pathology relies on histopathological tools to define visible internal structures and processes in understudied taxa like spiders. Histopathology involves the infiltration of tissues and organ structures with wax or resin, allowing for the visualisation of cellular anatomy and morphological structure, which can lead to the identification of abnormalities (e.g., pathology) and symbioses (e.g., parasites). In this study, southern African social spiders - Stegodyphus dumicola (Araneae: Eresidae) - were histologically prepared whole and their tissue appearances described (eyes, stomach, heart, ovaries, cuticle, stercoral pocket, chelicerae, book lungs, and silk gland). In addition to healthy tissues, an intranuclear, baculovirus-like pathology was identified. The availability of this material and whole-preparation method makes for a valuable histological resource, where few such resources currently exist for spiders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Despite advancements in science, researchers still face challenges in curing patients with malignancies. This health issue is linked to various risk factors, including alcohol consumption, age, sex, and infectious diseases. Among these, viral agents play a significant role in cancer-related health problems and are currently a subject of ongoing research. In this review, we summarize how several viruses-such as herpesviruses, human papillomavirus, hepatitis B virus, hepatitis C virus, and adenovirus-impact cancer signaling pathways through their effects on the tumor suppressor PTEN., Competing Interests: Declaration of Competing Interest There is no conflict, (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objective: To study the impact of nonpharmaceutical interventions implemented during the COVID-19 pandemic on the monthly incidence of sudden unexpected death in infancy (SUDI) cases overall and those with a viral or bacterial identification., Study Design: We conducted an interrupted time-series analysis using seasonally adjusted Poisson regression models from the French national prospective and multicenter SUDI registry, that included all SUDI cases below the age of 1 year who died from 2016 to 2021 in mainland France., Results: Of 998 SUDI cases analyzed, 750 were recorded during the prepandemic period (January 2016 through March 2020) and 248 during the NPI period (April 2020 through December 2021). We found a significant seasonal pattern of overall monthly SUDI incidence, with a peak observed periodically from November to February. The monthly SUDI incidence decreased significantly from the prepandemic to NPI periods (adjusted incidence rate ratio 0.83 [95% CI 0.72-0.96]). In particular, the monthly incidence of SUDI cases with a viral or bacterial identification decreased significantly, while no significant difference was found for SUDI cases without a viral or bacterial identification., Conclusions: Nonpharmaceutical interventions were associated with a significant change in the incidence of SUDI cases with a viral or bacterial identification. Further investigations are needed to analyze the pathophysiologic role of viruses and bacteria in the SUDI., Competing Interests: Declaration of Competing Interest The French SUDI registry receives main funding from AXA, France; MSDAvenir, France; Sanofi Pasteur-MSD, France; the French national public health agency (Santé Publique France), France; the National Institute of Health and Medical Research (Inserm), France; and 3 French parent associations (SA VIE, Naitre et Vivre, and Les Rires d'Anna); it also received gifts from private organizations and companies. This particular work was supported by the Fondation de France (Alliance “Tous unis contre le virus”, grant n°APHP220322). Funders were not involved in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication. No support from any organization for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work, and no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

As of 26 April 2024, the International Committee on Taxonomy of Viruses has registered 14690 virus species. Of these, only several dozen have been chemically and thermodynamically characterized. Every virus species is characterized by a specific empirical formula and thermodynamic properties - enthalpy, entropy and Gibbs energy. These physical properties are used in a mechanistic model of virus-host interactions at the cell membrane and in the cytoplasm. This review article presents empirical formulas and Gibbs energies for all major variants of SARS-CoV-2. This article also reports and suggests a mechanistic model of evolutionary changes, with the example of time evolution of SARS-CoV-2 from 2019 to 2024., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Human rhinoviruses (RV) are among the most frequent human pathogens. As major causative agents of common colds they originate serious socioeconomic problems and huge expenditure every year, and they also exacerbate severe respiratory diseases. No anti-rhinoviral drugs or vaccines are available so far. Antiviral drug design may benefit from an understanding of the role during the infectious cycle of the interactions in the virion between the capsid and the viral nucleic acid. The genomic RNA inside the human RV virion forms a dodecahedral cage made of 30 double-stranded RNA elements that interact with equivalent sites at the capsid inner wall. RNA dodecahedral cages also occur in distantly related insect and plant viruses. However, the functional role(s) of the interactions between any dodecahedral cage and the capsid remained to be established. Here we describe an extensive structure-function mutational analysis of the capsid-RNA dodecahedral cage interface in the RV virion, to dissect the role of the interactions between the capsid and the cage-forming RNA duplexes in: (i) infection by RV; (ii) virus biological fitness; (iii) virion assembly; (iv) virion stability; and (v) viral RNA uncoating. The results reveal that the capsid-bound dsRNA dodecahedral cage in the human RV virion is a multifunctional structural element. Two structurally overlapping subsets of RNA duplex-capsid interactions promote virus infectivity and biological fitness by respectively facilitating virion assembly or restraining the untimely, unproductive uncoating of the viral RNA genome. These results provide new insights into virion morphogenesis and genome uncoating, and have implications for antiviral drug design., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Viral infections have led to the deaths of millions worldwide and come with significant economic and social burdens. Emerging viral infections, as witnessed with coronavirus disease 2019 (COVID-19), can profoundly affect all aspects of human life, highlighting the imperative need to develop diagnostic, therapeutic, and effective control strategies in response. Numerous studies highlight the diverse applications of nanoparticles in diagnosing, controlling, preventing, and treating viral infections. Due to favorable and flexible physicochemical properties, small size, immunogenicity, biocompatibility, high surface-to-volume ratio, and the ability to combine with antiviral agents, gold nanoparticles (AuNPs) have shown great potential in the fight against viruses. The physical and chemical properties, the adjustability of characteristics based on the type of application, the ability to cross the blood-brain barrier, the ability to infiltrate cells such as phagocytic and dendritic cells, and compatibility for complexing with various compounds, among other features, transform AuNPs into a suitable tool for combating and addressing pathogenic viral agents through multiple applications. In recent years, AuNPs have been employed in various applications to fight viral infections. However, a comprehensive review article on the applications of AuNPs against viral infections has yet to be available. Given their versatility, AuNPs present an appealing option to address various gaps in combating viral infections. Hence, this review explores the attributes, antiviral properties, contributions to drug delivery, vaccine development, and diagnostic uses of AuNPs., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2025. Published by Elsevier Masson SAS.)

Lumpy skin disease (LSD), a viral disease of cattle, can be acute, subacute, or inactive. It is distinguished by fever and the abrupt emergence of firm, confined cutaneous nodules that usually necrotize. Similar lesions may occur in the skeletal muscles and the mucosae of the digestive and respiratory tracts. It is an enzootic, rapidly explorative, and sometimes fatal infection, characterized by multiple raised nodules on the skin of infected animals. LSDV has a large genome, it is employed as a vaccine carrier, generating a new complex with other viral genes by homologous recombination. This review summarizes our current knowledge of lumpy skin disease (LSD), its impact on animal health, host-pathogen interaction, etiology, signs or symptoms, prevention, and treatment strategies., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Yellow mealworm (Tenebrio molitor) larvae are increasingly recognized as a potential source of bioactive peptides due to their high protein content. Antimicrobial peptides from sustainable sources are a research topic of interest. This study aims to characterize the peptidome of T. molitor flour and an Alcalase-derived hydrolysate, and to explore the potential presence of antimicrobial peptides using in silico analyses, including prediction tools, molecular docking and parameter correlations., Results: T. molitor protein was hydrolysed using Alcalase, resulting in a hydrolysate (TMH10A) with a 10% degree of hydrolysis. The peptidome was analysed using LC-TIMS-MS/MS, yielding over 6000 sequences. These sequences were filtered using the PeptideRanker tool, selecting the top 100 sequences with scores >0.8. Bioactivity predictions indicated that specific peptides, particularly WLNSKGGF and GFIPYEPFLKKMMA, showed significant antimicrobial potential, particularly against bacteria, fungi and viruses. Correlations were found between antifungal activity and physicochemical properties such as net charge, hydrophobicity and isoelectric point., Conclusions: The study identified specific T. molitor-derived peptides with strong predicted antimicrobial activity through in silico analysis. These peptides, particularly WLNSKGGF and GFIPYEPFLKKMMA, might offer potential applications in food safety and healthcare. Further experimental validation is required to confirm their efficacy. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Introduction: It is widely accepted that the higher the number of medications prescribed and taken by an individual, the higher the risk of poor health outcomes. We have investigated whether polypharmacy and comorbidities conveyed more risk of adverse health outcomes following COVID-19 infection (as a paradigm of serious viral infections in general) in people with type 1 diabetes (T1DM) or type 2 diabetes (T2DM)., Methods: The Greater Manchester Care Record (GMCR) is an integrated database of electronic health records containing data collected from 433 general practices in Greater Manchester. Baseline demographic information (age, body mass index [BMI], gender, ethnicity, smoking status, deprivation index), hospital admission or death within 28 days of infection were extracted for adults (18+) diagnosed with either T1DM or T2DM., Results: The study cohort included individuals diagnosed as T1DM and T2DM separately. Across the Greater Manchester Region, a total of 145,907 individuals were diagnosed with T2DM and 9705 were diagnosed with T1DM. For the T2DM individuals, 45.2% were women and for the T1DM individuals, 42.7% were women. For T2DM, 16-20 medications (p = 0.005; odds ratio [OR] [95% confidence interval (CI) 2.375 [1.306-4.319]) and > 20 medications (p < 0.001; OR [95% CI] 3.141 [1.755-5.621]) were associated with increased risk of death following COVID-19 infection. Increased risk of hospital admissions in T2DM individuals was associated with 11 to 15 medications (p = 0.013; OR = 1.341 (95% CI) [1.063-1.692]). This was independent of comorbidities, metabolic and demographic factors. For T1DM, there was no association of polypharmacy with hospital admission. Additionally, respiratory, cardiovascular/cerebrovascular and gastrointestinal conditions were associated with increased risk of hospital admissions and deaths in T2DM (p < 0.001). Many comorbidities were common across both T1DM and T2DM., Conclusions: We have shown in T2DM an independent association of multiple medications taken from 11 upwards with adverse health consequences following COVID-19 infection. We also found that individuals with diabetes develop comorbidities that were common across both T1DM and T2DM. This study has laid the foundation for future investigations into the way that complex pharmacological interactions may influence clinical outcomes in people with T2DM., Competing Interests: Declarations. Conflict of Interest: Juhi K Gupta, Rathi Ravindrarajah, George Tilston, William Ollier, Darren M Ashcroft and Adrian H Heald have no conflicts of interest. Ethical Approval: This project was reviewed, and ethical approval for COVID-19 research was overseen by Health Innovation Manchester and granted by the Greater Manchester Care Record (GMCR) review board (ref: IDCR-RQ-046). This research was performed with anonymised data, in line with the Health Research Authority’s Governance arrangements for research ethics committees., (© 2024. The Author(s).)

Numerous studies highlight the essential role of type I interferon (IFN) responses in type 1 diabetes. The absence of type I IFN signaling is associated with a partial reduction of autoimmune diabetes incidence in LEW.1WR1 rats. We sought to delineate type I IFN-independent mechanisms that drive diabetes using type I IFN α/β receptor (IFNAR) knockout rats. Rats were treated with polyinosinic:polycytidylic acid plus Kilham rat virus to induce diabetes. Single-cell RNA-sequencing of islets and cytokine measurements in blood and spleen from prediabetic Ifnar1 -/- rats were employed to identify factors driving insulitis in the global absence of IFNAR signaling. Islet immune cells were enriched for Ccl4, Ccl5, and Ifng. In addition, interleukin-1 (IL-1) was increased in spleen, and IFN-γ was increased in serum from prediabetic Ifnar1 -/- rats. Based on these findings, rats were treated with a C-C chemokine receptor type 5 inhibitor, an IL-1 receptor antagonist, or a nucleotide-binding oligomerization domain-like receptor family pyrin-domain containing 3 inhibitor, none of which prevented diabetes. The Janus kinase inhibitor ruxolitinib, which blocks both type I and II interferon-driven signaling, completely prevented diabetes, but only when given for a sustained period starting from the time of induction. The tyrosine kinase 2 inhibitor deucravacitinib also prevented diabetes to a significant degree. We conclude that type I and II IFNs act in concert as the main drivers of autoimmune diabetes and that inhibition of downstream signaling events for both is required for disease prevention., Competing Interests: Declaration of competing interest The authors declare there are no competing interests., (Copyright © 2025. Published by Elsevier Ltd.)

Viruses represent a diverse pool of obligate parasites that infect virtually every known organism, as such, their study is incredibly valuable for a range of fields including public health, medicine, agriculture, and ecology, and the development of biomedical technologies. Having evolved over millions of years, each virus has a unique and often complicated biology, that must be characterized on a case-by-case basis, even between strains of the same taxon. Owing to its nanoscale spatial resolution, atomic force microscopy (AFM) represents a powerful tool for exploring virus biology, including structural features, kinetics of binding to host cell ligands, virion self-assembly, and budding behaviors. Through the availability of numerous chemistries and advances in imaging modes, AFM is able to explore the complex web of host-virus interactions and life-cycle at a single virus level, exploring features at the level of individual bonds and molecules. Due to the wide array of techniques developed and data analysis approaches available, AFM can provide information that cannot be furnished by other modalities, especially at a single virus level. Here, we highlight the unique methods and information that can be obtained through the use of AFM, demonstrating both its utility and versatility in the study of viruses. As the technology continues to rapidly evolve, AFM is likely to remain an integral part of research, providing unique and important insight into many aspects of virology., Competing Interests: The authors declare no conflict of interest.

Background: The causes of breast cancer are poorly understood. A potential risk factor is Epstein-Barr virus (EBV), a lifelong infection nearly everyone acquires. EBV-transformed human mammary cells accelerate breast cancer when transplanted into immunosuppressed mice, but the virus can disappear as malignant cells reproduce. If this model applies to human breast cancers, then they should have genome damage characteristic of EBV infection., Objective: This study tests the hypothesis that EBV infection predisposes one to breast cancer by causing permanent genome damage that compromises cancer safeguards., Methods: Publicly available genome data from approximately 2100 breast cancers and 25 ovarian cancers were compared to cancers with proven associations to EBV, including 70 nasopharyngeal cancers, 90 Burkitt lymphomas, 88 diffuse large B-cell lymphomas, and 34 gastric cancers. Calculation algorithms to make these comparisons were developed., Results: Chromosome breakpoints in breast and ovarian cancer clustered around breakpoints in EBV-associated cancers. Breakpoint distributions in breast and EBV-associated cancers on some chromosomes were not confidently distinguished (P>.05), but differed from controls unrelated to EBV infection. Viral breakpoint clusters occurred in high-risk, sporadic, and other breast cancer subgroups. Breakpoint clusters disrupted gene functions essential for cancer protection, which remain compromised even if EBV infection disappears. As CRISPR (clustered regularly interspaced short palindromic repeats)-like reminders of past infection during evolution, EBV genome fragments were found regularly interspaced between Piwi-interacting RNA (piRNA) genes on chromosome 6. Both breast and EBV-associated cancers had inactivated genes that guard piRNA defenses and the major histocompatibility complex (MHC) locus. Breast and EBV-associated cancer breakpoints and other variations converged around the highly polymorphic MHC. Not everyone develops cancer because MHC differences produce differing responses to EBV infection. Chromosome shattering and mutation hot spots in breast cancers preferentially occurred at incorporated viral sequences. On chromosome 17, breast cancer breakpoints that clustered around those in EBV-mediated cancers were linked to estrogen effects. Other breast cancer breaks affected sites where EBV inhibits JAK-STAT and SWI-SNF signaling pathways. A characteristic EBV-cancer gene deletion that shifts metabolism to favor tumors was also found in breast cancers. These changes push breast cancer into metastasis and then favor survival of metastatic cells., Conclusions: EBV infection predisposes one to breast cancer and metastasis, even if the virus disappears. Identifying this pathogenic viral damage may improve screening, treatment, and prevention. Immunizing children against EBV may protect against breast, ovarian, other cancers, and potentially even chronic unexplained diseases., (© Bernard Friedenson. Originally published in JMIRx Med (https://med.jmirx.org).)

Bats are the hosts of a wide variety of coronaviruses (CoVs) of the genera Alphacoronavirus and Betacoronavirus. The presence of more than one CoV species or strain in a single bat species greatly enhances the chance of genetic exchange among the CoVs, mainly through homologous recombination, and hence enhance the generation of novel CoV species or strains that may adapt to human or other animals and result in future epidemics. In this article, we review the evidence for co-circulation and/or co-infection of two or more CoVs in the same bat species, including co-infection with different strains of a CoV, co-circulation/co-infection of different alphaCoVs or betaCoVs, and co-circulation/co-infection of alphaCoVs and betaCoVs together. With next-generation sequencing, there has been a recent explosion of such discoveries. It is anticipated that countless more similar findings will be made in the near future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Ticks are important vectors of a wide range of pathogens with significant medical and veterinary importance. Different tick species occupy different habitats with an overall widespread geographical distribution. In addition to their role as reservoirs or vectors, ticks are involved in maintaining pathogens in the environment and among wild and domestic animals. In this study, tick species infesting wild animals, as well as collected from the environment and their pathogens reported in 17 countries in Africa between 2003 and 2023, were collected according to the PRISMA guidelines. Data on ticks resulted in a total of 40 different tick species from 35 different wild animal species. Among the ticks, 34 infectious agents were noted including parasitic ( Babesia , Theileria , Hepatozoon , Eimeria ), bacterial ( Anaplasma , Bartonella , Borrelia , Candidatus Midichloria mitochondrii, Candidatus Allocryptoplasma spp., Coxiella , Ehrlichia , Francisella , and Rickettsia ), and a surprisingly high diversity of viral pathogens (Bunyamwera virus, Crimean-Congo Haemorhagic Fever virus, Ndumu virus, Semliki Forest virus, Thogoto virus, West Nile virus). These results highlight the public health and veterinary importance of the information on tick-borne infections. This knowledge is essential to strive to implement programs for sustainable control of ticks and tick-borne diseases.

Introduction: Respiratory pathogens pose a complex challenge for public health systems. In the winter of 2023, multiple respiratory pathogens showed staggered epidemic waves. Additionally, co-infections involving various pathogens were observed, resulting in significant disease burdens. Understanding the epidemiological dynamics of these pathogens is essential for supporting public health systems in the prevention and control of respiratory infectious diseases., Methods: Respiratory samples were collected from patients in Beijing presenting with influenza-like symptoms to detect 27 respiratory pathogens using multiplex qPCR., Results: Four distinct epidemic waves were identified. The first wave was a pre-winter outbreak of Mycoplasma pneumoniae ( M. pneumoniae ). This was then followed by successive waves of influenza A and B viruses. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited a resurgence by the end of February 2024. Age-dependent susceptibility varied, with SARS-CoV-2 and influenza A/B peaking in the 30-40-year age group. Conversely, adenovirus, rhinovirus, M. pneumoniae , Moraxella catarrhalis ( M. catarrhalis ), and Haemophilus influenzae ( H. influenzae ) were more common in adolescents and the elderly. Furthermore, 18.8% of cases were identified as co-infections with more than two pathogens. H. influenzae was found to frequently co-infect with viral and bacterial pathogens., Conclusions: Respiratory pathogens exhibited different prevalence trends during the first influenza season following the COVID-19 pandemic. Influenza viruses showed a higher peak incidence and delayed seasonality. Moreover, the co-circulation of viral and bacterial infections increased the complexity of respiratory infections. Interestingly, staggered epidemic waves between SARS-CoV-2 and influenza A/B viruses were observed. Consequently, SARS-CoV-2 may become a seasonal virus, causing epidemics alongside influenza viruses. However, further research is needed to elucidate its epidemiological patterns. The co-circulation of these epidemic viruses and other respiratory pathogens underscores the need for enhanced diagnostic and intervention strategies, including vaccination campaigns., Competing Interests: No conflicts of interest., (Copyright © 2025 by Chinese Center for Disease Control and Prevention.)

Influenza virus infects millions each year, contributing greatly to human morbidity and mortality. Upon viral infection, pathogen-associated molecular patterns activate pattern recognition receptors on host cells, triggering an immune response. The CD209 protein family, homologs of DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin), is thought to modulate immune responses to viruses. The effects of the mouse functional DC-SIGN homolog CD209d/e on the lung immune responses during influenza viral infection are not known. Therefore, we generated mice that lack both CD209d and e isoforms to determine the role in influenza viral infection. We infected wild-type and CD209d/e gene-deficient (CD209d/e-/-) mice with influenza virus and measured the cellular response in bronchoalveolar lavage, the expression of proinflammatory cytokines, antiviral genes, toll-like receptors (TLRs) in the lung, and lung pathology. We found CD209d/e-/- mice had decreased viral burden, TLR3 and TLR9 expression, interferon response, macrophages in bronchoalveolar lavage, and parenchymal lung inflammation compared with control mice. We also found less influenza viral uptake in alveolar macrophages and bone marrow-derived macrophages isolated from CD209d/e-/- mice when compared with control mice. We further investigated the role CD209d/e by treating bone marrow-derived macrophages from control and CD209d/e-/- mice with TLR agonists. We found that lacking CD209d/e decreased the expression of TLR3, TLR9, RIG1, STAT1, and STAT2 compared with controls. Collectively these results show that CD209d/e plays an important role in viral sensing/uptake and inflammatory immune responses during influenza viral infection., (© The Author(s) 2025. Published by Oxford University Press on behalf of The American Association of Immunologists.)

Orthoflaviviruses are emerging arthropod-borne pathogens whose replication cycle is tightly linked to host lipid metabolism. Previous lipidomic studies demonstrated that infection with the closely related hepatitis C virus (HCV) changes the fatty acid (FA) profile of several lipid classes. Lipids in HCV-infected cells had more very long-chain and desaturated FAs and viral replication relied on functional FA elongation and desaturation. Here, we systematically analyzed the role of FA elongases and desaturases in infection models of the most prevalent pathogenic orthoflaviviruses, dengue (DENV), Zika (ZIKV), West Nile (WNV), yellow fever (YFV), and tick-borne encephalitis virus (TBEV). Knockdown of desaturases and elongases in Huh7 cells only marginally affected ZIKV, WNV, YFV, and TBEV replication, while DENV titers were strongly reduced. This was most prominent for enzymes involved in very long-chain fatty acid synthesis. In detail, knockdown of the FA elongase ELOVL4, which catalyzes ultra-long-chain FA synthesis, significantly reduced DENV titers, decreased the formation of replication intermediates, and lowered viral protein levels in DENV-infected hepatoma cells, suggesting a function of ELOVL4 in DENV RNA replication. In contrast, the activity of FA desaturase FADS2, rate-limiting in poly-unsaturated FA biosynthesis, is not involved in viral RNA replication or translation, but is essentially required for the formation of infectious DENV particles. Further, in immunocompetent immortalized microglial cells, FADS2 deletion additionally limits viral replication through increased expression of interferon-stimulated genes in response to DENV infection. Taken together, enzymes involved in very long-chain FA synthesis are critical for different steps of DENV replication., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Since the 1990s, the Pacific oyster Magallana gigas has faced significant mortality, which has been associated with the detection of the Ostreid Herpesvirus type 1 (OsHV-1). Due to the complex genomic architecture and the presence of multiple genomic isomers, short-read sequencing using Illumina method struggles to accurately assemble tandem and repeat regions and to identify and characterize large structural variations in the OsHV-1 genome. Third-generation sequencing technologies, as long-read real-time nanopore sequencing from Oxford Nanopore Technologies (ONT), offer new possibilities for OsHV-1 whole-genome analysis. Identification of the best method for extraction of high molecular weight (HMW) DNA and development of accurate bioinformatic pipelines for its characterization are now required. To this end, we evaluated and compared six HMW methods and one conventional DNA extraction kit for their ability to extract OsHV-1 DNA from M. gigas -infected tissues. We then evaluated the ability of ONT sequencing to produce an accurate OsHV-1 genome from both whole-genome and "adaptive sampling" (AS) sequencing approaches. Finally, we evaluated the efficiency of bioinformatics tools for de novo assembly and consensus calling to generate accurate OsHV-1 genomes. The HMW DNA extraction kit coupled with ONT sequencing and dedicated bioinformatics tools allowed us to produce accurate OsHV-1 genomes compared to those assembled using Illumina technology. The AS approach allowed up to 60% enrichment for viral data, and the long reads generated by ONT allowed the characterization of OsHV-1 isomers. Together with its portability, this sequencing shows great promise as a diagnostic tool for the characterization of unculturable aquatic viruses directly from host tissues.IMPORTANCEMany aquatic viruses threaten commercially valuable species and cause significant economic losses during outbreaks. To improve our understanding of the origin, transmission patterns and spread of these viruses, additional genomic data are essential. However, genomic characterization of unculturable large DNA viruses is a major challenge. In the present study, we have successfully evaluated the ability of ONT sequencing and adaptive sequencing (AS) to sequence and assemble the complete OsHV-1 genome. Our results show that it is now possible to sequence the whole genome of large DNA viruses directly from infected host tissue, without the need for prior in vitro propagation or prior laboratory steps for virus enrichment.

The within-host environment changes over circadian time and influences the replication and severity of viruses. Genetic knockout of the circadian transcription factors CRYPTOCHROME 1 and CRYPTOCHROME 2 ( CRY1 -/- ; CKO) leads to altered protein homeostasis and chronic activation of the integrated stress response (ISR). The adaptive ISR signalling pathways help restore cellular homeostasis by downregulating protein synthesis in response to endoplasmic reticulum overloading or viral infections. By quantitative mass spectrometry analysis, we reveal that many viral recognition proteins and type I interferon (IFN) effectors are significantly upregulated in lung fibroblast cells from CKO mice compared with wild-type (WT) mice. This basal 'antiviral state' restricts the growth of influenza A virus and is governed by the interaction between proteotoxic stress response pathways and constitutive type I IFN signalling. CKO proteome composition and type I IFN signature were partially phenocopied upon sustained depletion of CRYPTOCHROME (CRY) proteins using a small-molecule CRY degrader, with modest differential gene expression consistent with differences seen between CKO and WT cells. Our results highlight the crosstalk between circadian rhythms, cell-intrinsic antiviral defences and protein homeostasis, providing a tractable molecular model to investigate the interface of these key contributors to human health and disease.This article is part of the Theo Murphy meeting issue 'Circadian rhythms in infection and immunity'.CRY2 -/- ; CKO) leads to altered protein homeostasis and chronic activation of the integrated stress response (ISR). The adaptive ISR signalling pathways help restore cellular homeostasis by downregulating protein synthesis in response to endoplasmic reticulum overloading or viral infections. By quantitative mass spectrometry analysis, we reveal that many viral recognition proteins and type I interferon (IFN) effectors are significantly upregulated in lung fibroblast cells from CKO mice compared with wild-type (WT) mice. This basal 'antiviral state' restricts the growth of influenza A virus and is governed by the interaction between proteotoxic stress response pathways and constitutive type I IFN signalling. CKO proteome composition and type I IFN signature were partially phenocopied upon sustained depletion of CRYPTOCHROME (CRY) proteins using a small-molecule CRY degrader, with modest differential gene expression consistent with differences seen between CKO and WT cells. Our results highlight the crosstalk between circadian rhythms, cell-intrinsic antiviral defences and protein homeostasis, providing a tractable molecular model to investigate the interface of these key contributors to human health and disease.This article is part of the Theo Murphy meeting issue 'Circadian rhythms in infection and immunity'.

Green sea turtles are listed on the International Union for Conservation of Nature's Red List of Threatened Species. Thus, conservation efforts, including investigation of factors affecting the health of green sea turtles, are critical. Viral communities play vital roles in maintaining animal health. In the present study, shotgun metagenomics was used for the first time to survey viruses in the feces of green sea turtles. Most viral contigs were DNA viruses that mainly belonged to Caudoviricetes , followed by Crassvirales . Additionally, most of the viral contigs were not assigned to any known family or genus, implying a large knowledge gap in the taxonomy of green sea turtle gut viruses. Host prediction showed that most viruses were connected to two phyla: Bacteroidetes and Firmicutes . Furthermore, KEGG enrichment analysis showed that the viral genes were mainly involved in phage-associated and metabolic pathways. Phylogenetic tree reconstruction of Caudovirales terminase large-subunit (TerL) protein showed that most of the sequences were phylogenetically distant. This study expands our understanding of the viral diversity in green sea turtles. In particular, analysis of the virome RNA fraction is exceedingly important for investigating intestinal viromes; therefore, future studies could use metatranscriptomics to study RNA viruses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Li, Chen, Xia, Zhuang, Cong and Lian.)

Piscine orthoreovirus-1 and 3 (PRV-1, PRV-3) cause highly prevalent infection in cultured salmonids and can induce heart and skeletal muscle inflammation (HSMI) resulting in economic losses in aquaculture. However, to date, PRV-1 and PRV-3 have withstood replication in continuous cell lines. In this study, we used beating heart cell cultures obtained from different developmental stages of rainbow trout (Oncorhynchus mykiss) (RTC-L and RTC-A) and tested their ability to sustain replication of PRV-1 and PRV-3. Furthermore, we compared the replication pattern of the different viruses with those in the newly developed heart fibroblast cell line (RTH-F) and the traditional established rainbow trout gonad cell line (RTG-2). Neither RTCs nor RTH-F cell lines supported replication of PRV-1 and PRV-3. Comparative experiments showed varying susceptibility of the novel cultures to viral haemorrhagic septicaemia virus (VHSV), chum salmon reovirus (CSV), infectious pancreatic necrosis virus (IPNV), piscine myocarditis virus (PMCV), salmonid alphavirus 3 (SAV-3) and tilapia lake virus (TiLV), indicating their usability for work with multiple fish viruses. While confirming the difficulty of replicating PRV-1 and PRV-3, the results demonstrate the potential of novel heart-derived cell cultures as in vitro tools for studying fish viruses., (© 2025 The Author(s). Journal of Fish Diseases published by John Wiley & Sons Ltd.)