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Influenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here, we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997-2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection ynamics, presumably via heterosubtypic cross-immunity.

Tobacco mild green mosaic virus (TMGMV)-like nanocarriers were designed for gene delivery to plant cells. High aspect ratio TMGMVs were coated with a polycationic biopolymer, poly(allylamine) hydrochloride (PAH), to generate highly charged nanomaterials (TMGMV-PAH; 56.20 ± 4.7 mV) that efficiently load (1:6 TMGMV:DNA mass ratio) and deliver single-stranded and plasmid DNA to plant cells. The TMGMV-PAH were taken up through energy-independent mechanisms in Arabidopsis protoplasts. TMGMV-PAH delivered a plasmid DNA encoding a green fluorescent protein (GFP) to the protoplast nucleus (70% viability), as evidenced by GFP expression using confocal microscopy and Western blot analysis. TMGMV-PAH were inactivated (iTMGMV-PAH) using UV cross-linking to prevent systemic infection in intact plants. Inactivated iTMGMV-PAH-mediated pDNA delivery and gene expression of GFP in vivo was determined using confocal microscopy and RT-qPCR. Virus-like nanocarrier-mediated gene delivery can act as a facile and biocompatible tool for advancing genetic engineering in plants.

Background: COVID-19 caused closures of movement supporting environments such as gyms and schools in Canada. This study evaluated the association between Ontario parents' and children's physical activity levels across time during COVID-19, controlling for variables that were identified as significant predictors of children's and parents' physical activity (e.g., children's age, parents' employment status). Methods: Parents (n = 243; mean age = 38.8 y) of children aged 12 and under (n = 408; mean age = 6.3 y) living in Ontario, Canada completed 2 online surveys, the first between August and December 2020 and the second between August and December 2021. At baseline, parents were asked to recall prepandemic physical activity levels. To determine the association between parent and child physical activity during COVID-19, a cross-lagged model was estimated to determine the cross-sectional and longitudinal associations between parents' and children's physical activity across time. Results: Bivariate associations revealed that parents' and children's physical activity levels were significantly related during lockdown and postlockdown but not prelockdown. The autoregressive paths from prelockdown to during lockdown were significant for children (β = 0.53, P <.001) and parents (β = 1.058, P <.001) as were the autoregressive paths from during lockdown to postlockdown for children (β = 0.61, P <.001) and parents (β = 0.48, P <.001). In fully adjusted models, the cross-lagged association between parents' physical activity prelockdowns was significantly positively associated with their children's physical activity during lockdowns (β = 0.19, P =.013). Conclusions: Resources are needed to ensure that children and parents are obtaining sufficient levels of physical activity, particularly during a pandemic. [ABSTRACT FROM AUTHOR]

Global control of infectious diseases depends on the continuous development and deployment of diverse vaccination strategies. Currently available live-attenuated and killed virus vaccines typically take a week or longer to activate specific protection by the adaptive immunity. The mosquito-transmitted Nodamura virus (NoV) is attenuated in mice by mutations that prevent expression of the B2 viral suppressor of RNA interference (VSR) and consequently, drastically enhance in vivo production of the virus-targeting small-interfering RNAs. We reported recently that 2 d after immunization with live-attenuated VSR-disabled NoV (NoVΔB2), neonatal mice become fully protected against lethal NoV challenge and develop no detectable infection. Using Rag1-/- mice that produce no mature B and T lymphocytes as a model, here we examined the hypothesis that adaptive immunity is dispensable for the RNAi-based protective immunity activated by NoVΔB2 immunization. We show that immunization of both neonatal and adult Rag1-/- mice with live but not killed NoVΔB2 induces full protection against NoV challenge at 2 or 14 d postimmunization. Moreover, NoVΔB2-induced protective antiviral immunity is virus-specific and remains effective in adult Rag1-/- mice 42 and 90 d after a single-shot immunization. We conclude that immunization with the live-attenuated VSR-disabled RNA virus vaccine activates rapid and long-lasting protective immunity against lethal challenges by a distinct mechanism independent of the adaptive immunity mediated by B and T cells. Future studies are warranted to determine whether additional animal and human viruses attenuated by VSR inactivation induce similar protective immunity in healthy and adaptive immunity-compromised individuals.

When proteins evolve new activity, a concomitant decrease in stability is often observed because the mutations that confer new activity can destabilize the native fold. In the conventional model of protein evolution, reduced stability is considered a purely deleterious cost of molecular innovation because unstable proteins are prone to aggregation and are sensitive to environmental stressors. However, recent work has revealed that nonnative, often unstable protein conformations play an important role in mediating evolutionary transitions, raising the question of whether instability can itself potentiate the evolution of new activity. We explored this question in a bacteriophage receptor-binding protein during host-range evolution. We studied the properties of the receptor-binding protein of bacteriophage λ before and after host-range evolution and demonstrated that the evolved protein is relatively unstable and may exist in multiple conformations with unique receptor preferences. Through a combination of structural modeling and in vitro oligomeric state analysis, we found that the instability arises from mutations that interfere with trimer formation. This study raises the intriguing possibility that protein instability might play a previously unrecognized role in mediating host-range expansions in viruses.

Influenza D virus (IDV) utilizes bovines as a primary reservoir with periodical spillover to other hosts. We have previously demonstrated that IDV binds both 9-O-acetylated N-acetylneuraminic acid (Neu5,9Ac2) and 9-O-acetylated N-glycolylneuraminic acid (Neu5Gc9Ac). Bovines produce both Neu5,9Ac2 and Neu5Gc9Ac, while humans are genetically unable to synthesize Neu5Gc9Ac. 9-O-Acetylation of sialic acids is catalyzed by CASD1 via a covalent acetyl-enzyme intermediate. To characterize the role of Neu5,9Ac2 and Neu5Gc9Ac in IDV infection and determine which form of 9-O-acetylated sialic acids drives IDV entry, we took advantage of a CASD1 knockout (KO) MDCK cell line and carried out feeding experiments using synthetic 9-O-acetyl sialic acids in combination with the single-round and multi-round IDV infection assays. The data from our studies show that (i) CASD1 KO cells are resistant to IDV infection and lack of IDV binding to the cell surface is responsible for the failure of IDV replication; (ii) feeding CASD1 KO cells with Neu5,9Ac2 or Neu5Gc9Ac resulted in a dose-dependent rescue of IDV infectivity; and (iii) diverse IDVs replicated robustly in CASD1 KO cells fed with either Neu5,9Ac2 or Neu5Gc9Ac at a level similar to that in wild-type cells with a functional CASD1. These data demonstrate that IDV can utilize Neu5,9Ac2- or non-human Neu5Gc9Ac-containing glycan receptor for infection. Our findings provide evidence that IDV has acquired the ability to infect and transmit among agricultural animals that are enriched in Neu5Gc9Ac, in addition to posing a zoonotic risk to humans expressing only Neu5,9Ac2.IMPORTANCEInfluenza D virus (IDV) has emerged as a multiple-species-infecting pathogen with bovines as a primary reservoir. Little is known about the functional receptor that drives IDV entry and promotes its cross-species spillover potential among different hosts. Here, we demonstrated that IDV binds exclusively to 9-O-acetylated N-acetylneuraminic acid (Neu5,9Ac2) and non-human 9-O-acetylated N-glycolylneuraminic acid (Neu5Gc9Ac) and utilizes both for entry and infection. This ability in effective engagement of both 9-O-acetylated sialic acids as functional receptors for infection provides an evolutionary advantage to IDV for expanding its host range. This finding also indicates that IDV has the potential to emerge in humans because Neu5,9Ac2 is ubiquitously expressed in human tissues, including lung. Thus, results of our study highlight a need for continued surveillance of IDV in humans, as well as for further investigation of its biology and cross-species transmission mechanism.

Despite a substantial body of research, we lack fundamental understanding of the pathophysiology of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) including pulmonary and cardiovascular outcomes, in part due to limitations of murine models. Most models use transgenic mice (K18) that express the human (h) angiotensin converting enzyme 2 (ACE2), ACE2 knock-in (KI) mice, or mouse-adapted strains of SARS-CoV-2. Further, many SARS-CoV-2 variants produce fatal neurologic disease in K18 mice and most murine studies focus only on acute disease in the first 14 days post inoculation (dpi). To better enable understanding of both acute (14 dpi) infection phases, we describe the development and characterization of a novel non-lethal KI mouse that expresses both the ACE2 and transmembrane serine protease 2 (TMPRSS2) genes (hACE2/hTMPRSS2). The human genes were engineered to replace the orthologous mouse gene loci but remain under control of their respective murine promoters, resulting in expression of ACE2 and TMPRSS2 instead of their murine counterparts. After intranasal inoculation with an omicron strain of SARS-CoV-2, hACE2/hTMPRSS2 KI mice transiently lost weight but recovered by 7 dpi. Infectious SARS-CoV-2 was detected in nasopharyngeal swabs 1-2 dpi and in lung tissues 2-6 dpi, peaking 4 dpi. These outcomes were similar to those in K18 mice that were inoculated in parallel. To determine the extent to which hACE2/hTMPRSS2 KI mice are suitable to model pulmonary and cardiovascular outcomes, physiological assessments measuring locomotion, behavior and reflexes, biomonitoring to measure cardiac activity and respiration, and micro computed tomography to assess lung function were conducted frequently to 6 months post inoculation. Male but not female SARS-CoV-2 inoculated hACE2/hTMPRSS2 KI mice showed a transient reduction in locomotion compared to control saline treated mice. No significant changes in respiration, oxygen saturation, heart rate variability, or conductivity were detected in SARS-CoV-2 inoculated mice of either sex. When re-inoculated 6 months after the first inoculation, hACE2/hTMPRSS2 KI became re-infected with disease signs similar to after the first inoculation. Together these data show that a newly generated hACE2/hTMPRSS2 KI mouse can be used to study mild COVID-19.

Herpetic geometric glossitis is a unique morphologic variant of HSV (herpes simplex virus) type 1 infection on the dorsum of the tongue that presents as an extremely painful linear central lingual fissure with a branched pattern. in the center of the tongue; there is a branched pattern of fissures that extend bilaterally from the central linear fissure. Herpetic geometric glossitis has been reported in 11 patients; 8 of these individuals were immunocompromised. Medical conditions and immunosuppressive medication treatment (7 patients) or only medical disorders (3 patients) or neither (1 patient) were present. HSV type 1 infection was diagnosed by viral culture in (7 patients), Tzanck preparation (2 patients) or clinically (2 patients). Mucocutaneous HSV infection at non-lingual locations--including the lips, labial mucosa, face and chest--were observed in 5 patients. All patients' symptoms and lesions responded to treatment with oral antiviral therapy: acyclovir (9 patients), famciclovir (1 patient) or valacyclovir (1 patient). The lingual pain and dorsal tongue fissures completely resolved completely within two to 14 days. In summary, herpetic geometric glossitis is a unique HSV type 1 infection, usually in immunocompromised patients, that occurs on the dorsal tongue and responds completely after treatment with orally administered antiviral therapy.

The knife-cut sign is a distinctive manifestation of herpes simplex virus (HSV) type 1 or HSV type 2 infection that has been described in at least 10 immunocompromised patients. It appears as an extremely painful linear erosion or fissure in an intertriginous area such as the body folds beneath the breast, or within the abdomen, or in the inguinal region. Also, concurrent HSV infection at other mucocutaneous sites, or viscera, or both have been observed. The patients had medical conditions (at least 9 patients) and/or immunosuppressive drug therapy (6 patients). The diagnosis of HSV infection was confirmed by viral culture (8 patients), biopsy (4 patients), direct fluorescence antibody testing (3 patients), immunohistochemistry staining (2 patients), polymerase chain reaction (2 patients), or Western blot serologic assay (1 patient). Knife-cut sign-associated HSV infection is potentially fatal; three patients died. However, clinical improvement or complete healing occurred in the patients who received oral valacyclovir (1 patient), or intravenous acyclovir (2 patients), or intravenous acyclovir followed by foscarnet (1 patient). In summary, HSV infection associated with a positive the knife-cut sign is a potentially fatal variant of HSV infection that occurs in the intertriginous areas of immunocompromised patients and usually requires intravenous antiviral therapy.

Background: The Antarctic environment is susceptible to the introduction of non-native species due to its unique ecosystem, which has evolved under geographical isolation and extreme climatic conditions over an extended period. The recent introduction of the non-native winter crane fly, Trichocera maculipennis, to maritime Antarctica may pose a potential threat to the Antarctic ecosystem. In this study, we evaluated the possibility of the mechanical transmission of viruses by T. maculipennis. Methods: We assessed the potential for the mechanical transmission of viruses using next-generation sequencing (NGS), quantitative PCR (qPCR), and virus isolation methods from T. maculipennis (Tm)-related samples (Tm body-wash fluid and Tm body-ground samples) collected from habitats and sewage treatment facilities located at three research stations in Antarctica. Results: Virome analysis detected the genomic fragments of human adenovirus (AdV) and human endogenous retrovirus (HERV) in Tm-related samples. These viruses are commonly found in human feces. In addition, plant viruses, such as pepper mild mottle virus (PMMoV) and cucumber green mottle mosaic virus (CGMMV), both known indicators of enteric viruses, were identified in all Tm-related samples, likely originating from wastewater. However, the low quantities of AdV and HERV genomes detected in Tm-related samples through qPCR, coupled with the non-viability of AdV in virus isolation tests, indicate that T. maculipennis has limited potential for mechanical transmission under the conditions in the studies. Conclusions: Our study represents the first evaluation of the potential risk of non-native species serving as vectors for viral pathogens in Antarctica. Although the viruses detected were in relatively low quantities and non-viable, this study highlights the importance of further evaluating the risks associated with non-native species, particularly as the likelihood of their introduction increases to Antarctica due to climate change and increased human activity. [ABSTRACT FROM AUTHOR]

Objective: Pakistan has been seriously affected by the COVID-19 pandemic, with numerous waves of infection. Using different vaccine and booster doses was a key component to control and combat this pandemic. This study aims to monitor the heterologous and homologous booster vaccination doses that generate immune responses in healthy adults after 9 months of vaccination. Methods: In this cross-sectional, observational study a total of 173 samples were collected. Participants from both genders (Male and Female) between the ages of 18 to 25 years were enrolled for the study. Participants who had booster shots of homologous Sinopharm BBIBP CorV and heterologous Pfizer-BioNTech vaccines were included only, with the use of a Roche Cobas-e601 analyzer, the antibody titers in the blood serum were quantified by the ECLIA method. IBM SPSS 22 was utilized for descriptive statistical analysis and P< 0.05 was considered significant. Results: In this study the IgG antibody levels were measured against the full length of receptor binding domain (RBD) of the spike (S) protein. The mean antibody titer in the Pfizer group was 9764 ± 10976 U/mL and 5762 ± 4302 U/mL in the Sinopharm group. The Mean IgG antibody levels of the Pfizer-vaccinated group were significantly higher than the Sinopharm-vaccinated group (P=0.000, each). Comparing the Sinopharm BBIBP CorV booster dosage to the Pfizer booster, Pfizer BNT162b2demonstrated a stronger immune response. However, there were no immunological gender-specific significant differences. The administration of a third dosage of Pfizer BNT162b2 after two doses of BBIBP CorV Conclusion: The administration of a third dosage of Pfizer BNT162b2 after two doses of BBIBP-CorV is recommended to boost the humoral immune response in the general population while there was no gender-specific difference observed. More effectiveness can be attained by administering additional doses due to the antibody decay. [ABSTRACT FROM AUTHOR]

Diagnostic electron microscopy (EM) is indispensable in all cases of infectious diseases which deserve or profit from the detection of the entire pathogen (i.e. the infectious unit). The focus of its application has shifted during the last decades from routine diagnostics to diagnostics of special cases, emergencies and the investigation of disease pathogenesis. While the focus of application has changed, the methods remain more or less the same. However, since the number of cases for diagnostic EM has declined as the number of laboratories that are able to perform such investigations, the preservation of the present knowledge is important. The aim of this article is to provide a review of the methods and strategies which are useful for diagnostic EM related to infectious diseases in our days. It also addresses weaknesses as well as useful variants or extensions of established methods. The main techniques, negative staining and thin section EM, are described in detail with links to suitable protocols and more recent improvements, such as thin section EM of small volume suspensions. Sample collection, transport and conservation/inactivation are discussed. Strategies of sample examination and requirements for a proper recognition of structures are outlined. Finally, some examples for the actual application of diagnostic EM related to infectious diseases are presented. The outlook section will discuss recent trends in microscopy, such as automated object recognition by machine learning, regarding their potential in supporting diagnostic EM. [ABSTRACT FROM AUTHOR]

The red imported fire ant (RIFA) has made China its habitat for approximately 25 years, but few reports have described the species and amount of virus circulating in it. Researchers are currently exploring viruses associated with RIFAs as potential biological control agents against invasive ants. The present meta-transcriptome analysis revealed the virome of red imported fire ants in Guangdong, southern China, which included 17 viruses, including Solenopsis invicta virus 4-GD (SINV-4) and Guangdong Polycipiviridae ant virus 1 (GPAV1) in the Polycipiviridae family; Solenopsis invicta virus 1-GD (SINV-1), and Guangdong Dicistroviridae ant virus 2-3 (GDAV2-3) in the Dicistroviridae family; Guangdong Iflaviridae ant virus 4-9 (GIAV4-9) in the Iflaviridae family; Guangdong Parvoviridae ant virus 10 (GPAV10) in the Parvoviridae family; and Guangdong ant virus 11-15 (GAV11-15). A total of 15 novel viruses and 2 known viruses were identified in this study. These findings reveal the virome of red imported fire ants in Guangdong Province and present a different result from that of a similar study reported in the United States, providing more choices for potential classical biological control agents against red imported fire ants in China. [ABSTRACT FROM AUTHOR]

This article traces the influence of colonialism in South Korean viral outbreak films. It specifically interrogates the pathways viruses travel—from the Global South to the Global North—how such travel happens along colonial routes, and how such travel lays bare postcolonial conflicts between South Korea and, namely, the US empire. I introduce the notion of viral imperialism in my film analysis, a concept that implies the long tentacles of empire reaching from the Global North into the Global South, while also following along historically colonial routes that tap into existing narratives and fears of contagions. By weaving film analysis with the historical context of US empire-building in South Korea and the development of South Korean public health, I argue that these films offer a critique of empire as a process that is willing to sacrifice some (read Koreans) for the health and safety of the empire and, arguably, the world. [ABSTRACT FROM AUTHOR]

Background: Classical Swine Fever (CSF) is still one of the most economically important viral diseases of pigs. In endemic countries, the disease is controlled mostly through vaccination; hence, the availability of safe and effective vaccines is of utmost importance. Vaccines intended for application in developing countries must also be thermally stable, since the infrastructure needed to maintain a cold chain in those countries is usually lacking. Porvac® is a second-generation subunit marker vaccine against CSF that has demonstrates to be safe and protective. Previous studies have also shown that the vaccine is stable for 1 week at 37 oC and have a shelf life of at least 36 months at 2–8 oC. The aim of this work was to further explore the accelerated stability of Porvac® by assessing the physicochemical properties of the emulsion, and the safety and immunogenicity of the vaccine subjected to more drastic conditions of thermal stress: (1) 25 oC for 12 months; (2) 30oC and 37 oC for one month and (3) 15 days at 37 °C after the cap of the vials had been needle-punctured. Results: The vaccine subjected to all these conditions did not show significant changes in the physicochemical properties of the emulsion; did not produce local or systemic adverse reactions in pigs, and the chromatographic profile of the recovered antigen was preserved. All vaccinated swine developed neutralizing antibody titers ≥ 1:1000 at 28 days post vaccination. Conclusions: Porvac® is stable in all the experimental conditions tested, even after cap puncture, and retains the capacity to induce high titers of neutralizing antibodies, well above the threshold of protection. These results reinforce the robustness of the vaccine, and support its use as a very attractive alternative to modified live vaccines in developing countries endemic for CSF. [ABSTRACT FROM AUTHOR]

Implantation is the key initial complex stage of pregnancy. Several factors are involved in implantation, but acute and controlled inflammation has been shown to play as a key role. On the other hand, the role of viral infections in directly infecting blastocyst and trophoblast and inducing chronic and uncontrolled inflammation and disrupting microRNAs expression can make this review strongly attractive and practical. We aim to provide an overview of viral infections as the potential etiology of unsuccessful implantation pathophysiology through alteration of the cellular and molecular endometrial microenvironment. Based on our search, this is the first review to discuss the role of inflammation associated with viral infection in implantation failure. [ABSTRACT FROM AUTHOR]

Viral proteins that evade the host's innate immune response play a crucial role in pathogenesis, significantly impacting viral infections and potential therapeutic strategies. Identifying these proteins through traditional methods is challenging and time-consuming due to the complexity of virus-host interactions. Leveraging advancements in computational biology, we present VirusHound-II, a novel tool that utilizes machine learning techniques to predict viral proteins evading the innate immune response with high accuracy. We evaluated a comprehensive range of machine learning models, including ensemble methods, neural networks, and support vector machines. Using a dataset of 1337 viral proteins known to evade the innate immune response (VPEINRs) and an equal number of non-VPEINRs, we employed pseudo amino acid composition as the molecular descriptor. Our methodology involved a tenfold cross-validation strategy on 80% of the data for training, followed by testing on an independent dataset comprising the remaining 20%. The random forest model demonstrated superior performance metrics, achieving 0.9290 accuracy, 0.9283 F1 score, 0.9354 precision, and 0.9213 sensitivity in the independent testing phase. These results establish VirusHound-II as an advancement in computational virology, accessible via a user-friendly web application. We anticipate that VirusHound-II will be a crucial resource for researchers, enabling the rapid and reliable prediction of viral proteins evading the innate immune response. This tool has the potential to accelerate the identification of therapeutic targets and enhance our understanding of viral evasion mechanisms, contributing to the development of more effective antiviral strategies and advancing our knowledge of virus-host interactions. [ABSTRACT FROM AUTHOR]

Viral oncoproteins play crucial roles in transforming normal cells into cancer cells, representing a significant factor in the etiology of various cancers. Traditionally, identifying these oncoproteins is both time-consuming and costly. With advancements in computational biology, bioinformatics tools based on machine learning have emerged as effective methods for predicting biological activities. Here, for the first time, we propose an innovative approach that combines Generative Adversarial Networks (GANs) with supervised learning methods to enhance the accuracy and generalizability of viral oncoprotein prediction. Our methodology evaluated multiple machine learning models, including Random Forest, Multilayer Perceptron, Light Gradient Boosting Machine, eXtreme Gradient Boosting, and Support Vector Machine. In ten-fold cross-validation on our training dataset, the GAN-enhanced Random Forest model demonstrated superior performance metrics: 0.976 accuracy, 0.976 F1 score, 0.977 precision, 0.976 sensitivity, and 1.0 AUC. During independent testing, this model achieved 0.982 accuracy, 0.982 F1 score, 0.982 precision, 0.982 sensitivity, and 1.0 AUC. These results establish our new tool, VirOncoTarget, accessible via a web application. We anticipate that VirOncoTarget will be a valuable resource for researchers, enabling rapid and reliable viral oncoprotein prediction and advancing our understanding of their role in cancer biology. [ABSTRACT FROM AUTHOR]

Background: Many patients experience persistent symptoms after COVID-19, a syndrome referred to as Long COVID (LC). The goal of this study was to identify novel new or worsening comorbidities self-reported in patients with LC. Methods: Patients diagnosed with LC (n = 732) at the Mayo Long COVID Care Clinic in Rochester, Minnesota and Jacksonville, Florida were sent questionnaires to assess the development of new or worsening comorbidities following COVID-19 compared to patients with SARS-CoV-2 that did not develop LC (controls). Both groups were also asked questions screening for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), generalized joint hypermobility (GJH) and orthostatic intolerance. 247 people with LC (33.7%) and 40 controls (50%) responded to the surveys. Results: In this study LC patients averaged 53 years of age and were predominantly White (95%) women (75%). The greatest prevalence of new or worsening comorbidities following SARS-CoV-2 infection in patients with LC vs. controls reported in this study were pain (94.4% vs. 0%, p < 0.001), neurological (92.4% vs. 15.4%, p < 0.001), sleep (82.8% vs. 5.3%, p < 0.001), skin (69.8% vs. 0%, p < 0.001), and genitourinary (60.6% vs. 25.0%, p = 0.029) issues. 58% of LC patients screened positive for ME/CFS vs. 0% of controls (p < 0.001), 27% positive for GJH compared to 10% of controls (p = 0.026), and a positive average score of 4.0 on orthostatic intolerance vs. 0 (p < 0.001). The majority of LC patients with ME/CFS were women (77%). Conclusion: We found that comorbidities across 12 surveyed categories were increased in patients following SARS-CoV-2 infection. Our data also support the overlap of LC with ME/CFS, GJH, and orthostatic intolerance. We discuss the pathophysiologic, research, and clinical implications of identifying these conditions with LC. [ABSTRACT FROM AUTHOR]

Bacterial and viral infections cause a huge burden to healthcare settings worldwide, and mortality rates associated with infectious microorganisms have remained high in recent decades. Despite tremendous efforts and resources worldwide to explore diagnostic biomarkers, rapid and easily assayed indicators for the diagnosis of bacterial and viral infections remain a challenge. B7 homolog 3 (B7-H3), a member of the B7 family of immunoregulatory proteins, is overexpressed in patients with septicemia, meningitis, pneumonia, and hepatitis. Therefore, B7-H3 could be used as a potential clinical indicator and therapeutic target for bacterial and viral infections caused by H. pylori, S. pneumoniae, M. pneumoniae, hepatitis B virus (HBV), viral hemorrhagic septicemia virus (VHSV), respiratory syncytial virus (RSV), and human immunodeficiency virus (HIV). Moreover, the interplay between infectious microorganisms and B7-H3 and exploration of the functional roles of the B7-H3 molecule could aid in the development of novel strategies for disease diagnosis and immunotherapy. [ABSTRACT FROM AUTHOR]

Viruses are intracellular parasites that utilize organelles, signaling pathways, and the bioenergetics machinery of the cell to replicate the genome and synthesize proteins to build up new viral particles. Mitochondria are key to supporting the virus life cycle by sustaining energy production, metabolism, and synthesis of macromolecules. Mitochondria also contribute to the antiviral innate immune response. Here, we describe the different mechanisms involved in virus–mitochondria interactions. We analyze the effects of viral infections on the metabolism of glucose in the Warburg phenotype, glutamine, and fatty acids. We also describe how viruses directly regulate mitochondrial function through modulation of the activity of the electron transport chain, the generation of reactive oxygen species, the balance between fission and fusion, and the regulation of voltage-dependent anion channels. In addition, we discuss the evasion strategies used to avoid mitochondrial-associated mechanisms that inhibit viral replication. Overall, this review aims to provide a comprehensive view of how viruses modulate mitochondrial function to maintain their replicative capabilities. [ABSTRACT FROM AUTHOR]

Mouse alveolar macrophages actively patrol the alveolar airspace and mask microbial antigens to limit damaging inflammation. Restraining human neutrophil expansion during viral upper respiratory infections can avoid excessive inflammation and prevent worsened clinical outcomes. The role and landscape of type I and type III interferons during human viral respiratory infections is context, age, and anatomical region dependent. Human lungs contain long-lived tissue-resident memory T and B cells with diverse phenotypes and functions. To preserve constant air exchange and host survival, the immune system of the mammalian respiratory tract is required to balance its capacity to tolerate commensal microorganisms with protection against pathogens, while avoiding excessive and damaging inflammation. These immune functions are further influenced by the highly divergent anatomical and functional characteristics of the upper airways, trachea, and lungs. New research offers key insights into mechanisms of immune system adaptation to each unique environment, increasing our understanding of the pathogenesis of respiratory infection and (excessive) inflammation. The respiratory tract is exposed to infection from inhaled pathogens, including viruses, bacteria, and fungi. So far, a comprehensive assessment that integrates common and distinct aspects of the immune response along different areas of the respiratory tract has been lacking. Here, we discuss key recent findings regarding anatomical, functional, and microbial factors driving regional immune adaptation in the mammalian respiratory system, how they differ between mice and humans, and the similarities and differences with the gastrointestinal tract. We demonstrate that, under evolutionary pressure, mammals evolved spatially organized immune defenses that vary between the upper and lower respiratory tract. Overall, we propose that the functional specialization of the immune response along the respiratory tract has fundamental implications for the management of infectious or inflammatory diseases. [ABSTRACT FROM AUTHOR]

While Dicer plays an important antiviral role through the RNAi pathway in plants and invertebrates, its contribution to antiviral immunity in vertebrates and more specifically mammals is more controversial. The apparent limited RNAi activity in mammalian cells has been attributed to the reduced long dsRNA processive activity of mammalian Dicer, as well as a functional incompatibility between the RNAi and IFN pathways. Why Dicer has lost this antiviral activity in the profit of the IFN pathway is still unclear. We propose that the primary direct antiviral activity of Dicer has been functionally replaced by other sensors in the IFN pathway, leading to its specialization toward microRNA maturation. As a result, Dicer can regulate the innate immune response and prevent basal activation of the IFN pathway in mammals. Here, we discuss this hypothesis, highlighting how the adaptation of the helicase domain of mammalian Dicer may be key to this process. [ABSTRACT FROM AUTHOR]

During virus infection, many host proteins are redirected from their normal cellular roles to restrict and terminate infection. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are cellular RNA‐binding proteins critical to host nucleic acid homeostasis, but can also be involved in the viral infection process, affecting virus replication, assembly and propagation. It has become evident that hnRNPs play important roles in modulation of host innate immunity, which provides critical initial protection against infection. These novel findings can potentially lead to the leveraging of hnRNPs in antiviral therapies. We review hnRNP involvement in antiviral innate immunity, in humans, mice and other animals, and discuss hnRNP targeting as a potential novel antiviral therapeutic. [ABSTRACT FROM AUTHOR]

Highly pathogenic avian influenza has emerged as a global menace over the past decades, posing a dramatic threat to birds worldwide, and its spread is of great concern to both conservationists and health authorities. In the 2022 breeding season, the Sandwich Tern Thalasseus sandvicensis was affected by a northwestern Europe-wide pandemic of the highly pathogenic avian influenza A (strain H5N1). This note reports on the occurrence of avian influenza in Sandwich Terns breeding in the Lagoon of Venice (Italy) in 2023 where the outbreak exterminated all chicks, but spared the adults. [ABSTRACT FROM AUTHOR]

Infertility affects approximately one‐sixth of couples worldwide, with male factors contributing to half of all cases. However, infections, particularly those of reproductive tract, are increasingly recognized as important contributors to male infertility. Therefore, in this meta‐analysis, we focused on the impact of various viral infections on male infertility. We searched PubMed, Embase, Web of Science and Cochrane Library on 20 October 2023. And included 135 studies involving 30,298 men of reproductive age. We found that the human papilloma virus (HPV)‐infected group had a significantly higher DNA fragmentation index (DFI) than the non‐infected group, with a mean difference (MD) of 5.64 (95% CI: 3.74–7.54). Conversely, the HPV‐infected group had significantly lower sperm count, concentration, viability and normal morphology. Other viruses that affect semen quality include hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). HBV significantly decreased fertilization rate, with an odds ratio (OR) of 0.86 (95% CI: 0.76–0.99). HPV associated with lower clinical pregnancy rate (OR: 0.31 [95% CI: 0.16–0.62]) and higher miscarriage rate (OR: 5.28 [95% CI: 2.02–13.78]). Additionally, the fertility treatment group had a significantly higher rate of HPV infection (OR: 1.85 [95% CI: 1.10–3.12]) and adeno‐associated virus (AAV) infection (OR: 8.49 [95% CI: 2.66–27.10]) than the fertility group. Conclusively, most viral infections affect semen quality, while HBV and HPV may affect assisted reproductive technology (ART) outcomes. HPV and AAV are risk factors for infertility. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) poses a significant threat to domestic pigs and wild boar (Sus scrofa) populations, with the current epidemiological situation more critical than ever. The disease has spread across five continents, causing devastating losses in the swine industry. Although extensive research efforts are ongoing to develop an effective and safe vaccine, this goal remains difficult to achieve. Among the potential vaccine candidates, live attenuated viruses (LAVs) have emerged as the most promising option due to their ability to provide strong protection against experimental challenges. However, ASF virus (ASFV) is highly diverse, with genetic and phenotypic variations across different isolates, which differ in virulence. This study highlights the limitations of a natural LAV strain (Lv17/WB/Rie1), which showed partial efficacy against a highly virulent and partially heterologous isolate (Arm07; genotype II). However, the LAV's effectiveness was incomplete when tested against a more phylogenetically distant virus (Ken06.Bus; genotype IX). These findings raise concerns about the feasibility of developing a universal vaccine for ASFV in the near future, emphasizing the urgent need to assess the protective scope of LAV candidates across different ASFV isolates to better define their limitations. [ABSTRACT FROM AUTHOR]

Many types of viruses infect insects and other arthropods. In contrast, little is known about how arthropods sense viruses, although several innate immune pathways including Toll have antiviral functions. Large DNA viruses in the family Baculoviridae are used to control a number of pest insects. Here, we studied Spodoptera litura and Autographa californica multiple nucleopolyhedrovirus (AcMNPV) to test the hypothesis that one or more myeloid differentiation-like (ML) proteins and Toll family members sense baculoviruses. We identified 11 ML and 12 Toll genes in the S. litura genome. A series of experiments indicated that S. litura ML protein 11 (SlML-11) binds the budded form of AcMNPV and partners with S. litura Toll5 (SlToll5). SlML-11 also bound sphingomyelin (SPM), which is a component of the virion envelope. Disabling SlML-11 and SlToll5 increased susceptibility to infection, while priming larvae with SPM reduced susceptibility as measured by increased survival to the adult stage and clearance of AcMNPV from individuals that emerged as adults. We conclude that SPM is a pathogen-associated molecular pattern molecule while SlML-11 and SlToll5 interact to function as a pattern recognition receptor that senses AcMNPV. [ABSTRACT FROM AUTHOR]

Background: Human rhinovirus (HRV), traditionally recognized as the primary etiological agent of the common cold, has become the second most important viral agent in bronchopulmonary conditions, such as pneumonia and asthma exacerbations. During the COVID‐19 pandemic, several viruses exhibited changes in their epidemiological behavior. This study aims to evaluate the clinical and epidemiological characteristics of children with HRV pneumonia before and during the pandemic in Mexico. Methods: A comparative ambispective longitudinal epidemiological study of two cohorts (prepandemic and pandemic periods) was carried out. Two databases were compared: one from 2010 to 2013 and the other from 2021 to 2023. Children under 5 years of age diagnosed with HRV pneumonia were included. Student's t‐test, χ2 tests, and logistic regression were used to assess risk factors associated with severe pneumonia. Incidence density was calculated as HRV cases per 10 new cases of pneumonia per month for each year. Results: During the pandemic, the age of presentation shifted from 5 months to 16 months. There was a higher incidence of HRV pneumonia in children during the pandemic, particularly in the second half of 2021, with a peak in July and August. In addition, there was an increase in severity (53% vs. 63%, p = 0.006) and coinfections (51.3% vs. 76% p < 0.001). A higher prevalence of all risk factors was observed in the second cohort. Conclusions: During the pandemic, a shift toward older age, a higher percentage of coinfections, and increased severity associated to HRV pneumonia were observed. These findings highlight the need for the development and implementation of targeted prevention and treatment measures for HRV. [ABSTRACT FROM AUTHOR]

The Nipah Virus (NiV) was discovered in 1999 in the Sungai Nipah region of Malaysia. It is one of many emerging bat-borne zoonotic viruses that threaten global health security. The Pteropus fruit bats are identified as the natural reservoirs for the virus. NiV belongs to the family of Paramyxoviridae and is mostly present in locations surrounded by water, vegetation, and controlled or protected religious areas. To date, cases of NiV have been identified in Southeast Asian regions, with the highest number of cases in Bangladesh, totalling 305, with a fatality rate of 65%. The highest mortality has been observed in the Indian region, at 73%. NiV is an emerging zoonotic disease that needs to be focused on. The median incubation period is 9.5 days and the clinical features primarily lead to either progressive encephalitis or Acute Respiratory Distress Syndrome. The diagnosis is conducted in Bio-safety level 3 or level 4 labs through Polymerase chain reaction. Human nasal swabs, throat swabs, urine, blood, and cerebrospinal fluid (CSF) are collected for diagnostic purposes. At present, there is no approved treatment or vaccine for the prevention of the disease. However, research on a vaccine against NiV is being investigated, and a subunit vaccine with NiV-G protein is found to produce potential efficacy. An outbreak in Kerala, a state in India, led to the implementation of an action plan involving lead agencies to combat the sudden surge of the virus. In the current scenario, appropriate preventive strategies are more effective in controlling the virus. However, emphasis should be placed on affordable and efficient diagnostic methods, treatment options, and vaccines to better manage the virus, considering the highest fatality caused by the virus. [ABSTRACT FROM AUTHOR]

Neurotropic pathogens, notably, herpesviruses, have been associated with significant neuropsychiatric effects. As a group, these pathogens can exploit molecular mimicry mechanisms to manipulate the host central nervous system to their advantage. Here, we present a systematic computational approach that may ultimately be used to unravel protein–protein interactions and molecular mimicry processes that have not yet been solved experimentally. Toward this end, we validate this approach by replicating a set of pre-existing experimental findings that document the structural and functional similarities shared by the human cytomegalovirus-encoded UL144 glycoprotein and human tumor necrosis factor receptor superfamily member 14 (TNFRSF14). We began with a thorough exploration of the Homo sapiens protein database using the Basic Local Alignment Search Tool (BLASTx) to identify proteins sharing sequence homology with UL144. Subsequently, we used AlphaFold2 to predict the independent three-dimensional structures of UL144 and TNFRSF14. This was followed by a comprehensive structural comparison facilitated by Distance-Matrix Alignment and Foldseek. Finally, we used AlphaFold-multimer and PPIscreenML to elucidate potential protein complexes and confirm the predicted binding activities of both UL144 and TNFRSF14. We then used our in silico approach to replicate the experimental finding that revealed TNFRSF14 binding to both B- and T-lymphocyte attenuator (BTLA) and glycoprotein domain and UL144 binding to BTLA alone. This computational framework offers promise in identifying structural similarities and interactions between pathogen-encoded proteins and their host counterparts. This information will provide valuable insights into the cognitive mechanisms underlying the neuropsychiatric effects of viral infections. [ABSTRACT FROM AUTHOR]

Understanding the structure and function of bioelectric materials is challenging due to the complex nature of biomaterials and a lack of appropriate tools. The precisely defined structures and genetic tunability of viruses provide an excellent model system to investigate bioelectrical behavior in biomaterials. This study presents the molecular mechanisms of piezoelectricity in the M13 bacteriophage (phage) under various mechanical stresses for bio‐piezoelectric generation. A computational approach is used to calculate the piezoelectric tensors of the M13 phage and quantify its direction‐dependent dipole moments. By computationally designing negatively charged residues on the phage surface, the surface charge density is enhanced to 16.7 µC cm−2. Using genetic engineering, phages are experimentally designed with different charges and tail structures to create model phage nanostructures, including individual phages, vertically standing phage films, and horizontally aligned phage films. Their vertical, horizontal, and shear‐mode piezoelectric properties are then measured using scanning probe microscopy techniques. The resulting phage‐based piezoelectric energy generators exhibit an effective piezoelectric coefficient of 15.4 pm V−1 and a power density of 4.2 µW cm−2. This phage‐based bioengineering approach provides a versatile platform for investigating fundamental mechanisms of bioelectricity and designing bioelectric materials for applications in energy harvesting, biomemory, and biosensors. [ABSTRACT FROM AUTHOR]

There is clinical evidence showing that the Pelargonium sidoides root extract EPs 7630 is a safe and effective treatment for a range of acute infectious respiratory illnesses. Moreover, EPs 7630 has been shown to reduce the use of antibiotics, which is important in the context of rising antibiotic resistance levels. A wide range of mechanisms appears to contribute to the beneficial effects of EPs 7630, e.g. antibacterial, antiviral, immunomodulatory, and epithelial barrier effects. This broad spectrum of pharmacological activities seems to enable the clinical activity of EPs 7630 against multiple respiratory infections. In particular, the combination of antiviral and immunomodulatory effects may enable EPs 7630 to tackle acute viral respiratory infections both in early stages of the disease process, which are driven by virus replication, as well as in later stages, which are caused by an overshooting immune response. Hence, EPs 7630 is a prime example of a plant extract with evidence-based clinical efficacy, including a solid understanding of the underlying mechanisms of action. The example of EPs 7630 demonstrates that plant extracts have a potential role as evidence-based clinical treatments and that they deserve pre-clinical and clinical testing and investigation in the same way as any other drug class. [ABSTRACT FROM AUTHOR]

Viral encephalitis is characterized by a series of immunological reactions that can control virus infection in the brain, but dysregulated responses may cause excessive inflammation and brain damage. Microglia are brain-resident myeloid cells that are specialized in surveilling the local CNS environment and in case of viral brain infection they contribute to the control of the infection and to restriction of viral dissemination. Here, we report that after exposure to neurotropic vesicular stomatitis virus (VSV), murine in vitro microglia cultures showed rapid upregulation of a broad range of pro-inflammatory and antiviral genes, which were stably expressed over the entire 8 h infection period. Additionally, a set of immunomodulatory genes was upregulated between 6 and 8 h post infection. In microglia cultures, the induction of several immune response pathways including cytokine responses was dependent on mitochondrial antiviral-signaling protein (MAVS). Consequently, in Mavs-deficient microglia the control of virus propagation failed as indicated by augmented virus titers and the accumulation of viral transcripts. Thus, in the analyzed in vitro system, MAVS signaling is critically required to achieve full microglia activation and to mediate profound antiviral effects. In Mavs-deficient mice, intranasal VSV instillation caused higher disease severity than in WT mice and virus dissemination was noticed beyond the olfactory bulb. Virus spread to inner regions of the olfactory bulb, i.e., the granular cell layer, correlated with the recruitment of highly inflammatory non-microglia myeloid cells into the olfactory bulb in Mavs−/− mice. Furthermore, increased cytokine levels were detected in the nasal cavity, the olfactory bulb and in other brain regions. Thus, microglial MAVS signaling is critically needed for virus sensing, full microglia activation, and for orchestration of protective immunity in the virus-infected CNS. [ABSTRACT FROM AUTHOR]

Probe-based nucleic acid enrichment represents an effective route to enhance the detection capacity of next-generation sequencing (NGS) in a set of clinically diverse and relevant microbial species. In this study, we assessed the effect of the enrichment-based sequencing on identifying respiratory infections using tiling RNA probes targeting 76 respiratory pathogens and sequenced using both Illumina and Oxford Nanopore platforms. Forty respiratory swab samples pre-tested for a panel of respiratory pathogens by qPCR were used to benchmark the sequencing data. We observed a general improvement in sensitivity after enrichment. The overall detection rate increased from 73 to 85% after probe capture detected by Illumina. Moreover, enrichment with probe sets boosted the frequency of unique pathogen reads by 34.6 and 37.8-fold for Illumina DNA and cDNA sequencing, respectively. This also resulted in significant improvements on genome coverage especially in viruses. Despite these advantages, we found that library pooling may cause reads mis-assignment, probably due to crosstalk issues arise from post-capture PCR and from pooled sequencing, thus increasing the risk of bleed-through signal. Taken together, an overall improvement in the breadth and depth of pathogen coverage is achieved using enrichment-based sequencing method. For future applications, automated library processing and pooling-free sequencing could enhance the precision and timeliness of probe enrichment-based clinical metagenomics. [ABSTRACT FROM AUTHOR]

Mitochondria, the cellular powerhouses with bacterial evolutionary origins, play a pivotal role in maintaining neuronal function and cognitive health. Several viruses have developed sophisticated mechanisms to target and disrupt mitochondrial function which contribute to cognitive decline and neurodegeneration. The interplay between viruses and mitochondria might be traced to their co-evolutionary history with bacteria and may reflect ancient interactions that have shaped modern mitochondrial biology. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis and bone fractures affect health and quality of life. Since bone disease is multifactorial, identifying risk factors is key in prevention. There are multiple reports on how viral hepatitis, especially chronic hepatitis B (CHB) and chronic hepatitis C (CHC), are affecting bone disease, but results vary. Here, we analyzed the potential association between CHB/CHC and osteoporosis or bone fractures in a large outpatient cohort in Germany. Methods: We included 3136 outpatients with CHB and 15,608 matched non-hepatitis individuals as well as 2867 outpatients with CHC and 14,335 matched non-hepatitis individuals from the Disease Analyzer Database between 2005 and 2022. The main outcome was the 5-year cumulative incidence of osteoporosis and bone fractures as a function of either CHB or CHC. Results: Within 5 years of the index date, 2.9% vs. 1.6% of patients with and without CHB were diagnosed with osteoporosis (p = 0.001) and 1.0% vs. 0.4% were diagnosed with bone fractures (p < 0.001). Moreover, 3.3% of CHC patients and 2.2% of individuals without hepatitis C were diagnosed with osteoporosis (p = 0.002). In Cox regression analyses, CHB was significantly associated with an increased risk for osteoporosis (HR: 1.76) and fractures (HR:2.43) and CHC with osteoporosis (HR: 1.54). For both CHB and CHC, the association with osteoporosis was restricted to the female subgroup. Conclusions: CHB and CHC are associated with osteoporosis in women. CHB in male patients is associated with a higher risk of fractures. More research is needed to understand the underlying pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Individuals with pancreatic-related health conditions usually show lower diversity and different composition of bacterial and viral species between the gut and oral microbiomes compared to healthy individuals. We performed a thorough microbiome analysis, using deep shotgun sequencing of stool and saliva samples obtained from patients with chronic pancreatitis (CP), pancreatic ductal adenocarcinoma (PDAC), and healthy controls (HCs).We observed similar microbiota composition at the species level in both the gut and oral samples in PDAC patients compared to HCs, among which the most distinctive finding was that the abundance of oral-originated Fusobacterium nucleatum species did not differ between the oral and the gut samples. Moreover, comparing PDAC patients with HCs, Klebsiella oxytoca was significantly more abundant in the stool samples of PDAC patients, while Streptococcus spp. showed higher abundance in both the oral and stool samples of PDAC patients. Finally, the most important finding was the distinctive gut phage–bacterial interactome pattern among PDAC patients. CrAssphages, particularly Blohavirus, showed mutual exclusion with K. oxytoca species, while Burzaovirus showed co-occurrence with Enterobacteriaceae spp., which have been shown to be capable of inducing DNA damage in human pancreatic cells ex vivo. The interactome findings warrant further mechanistic studies, as our findings may provide new insights into developing microbiota-based diagnostic and therapeutic methods for pancreatic diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSIONS 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.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.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. [ABSTRACT FROM AUTHOR]

The proteasome plays a crucial role in cellular homeostasis by degrading misfolded, damaged, or unnecessary proteins. Understanding the regulatory mechanisms of proteasome activity is vital, particularly the interaction with activators containing the hydrophobic-tyrosine-any amino acid (HbYX) motif. Here, we present ProEnd, a comprehensive database designed to identify and catalog HbYX motif-containing proteins across the tree of life. Using a simple bioinformatics pipeline, we analyzed approximately 73 million proteins from 22,000 reference proteomes in the UniProt/SwissProt database. Our findings reveal the widespread presence of HbYX motifs in diverse organisms, highlighting their evolutionary conservation and functional significance. Notably, we observed an interesting prevalence of these motifs in viral proteomes, suggesting strategic interactions with the host proteasome. As validation two novel HbYX proteins found in this database were experimentally tested by pulldowns, confirming that they directly interact with the proteasome, with one of them directly activating it. ProEnd's extensive dataset and user-friendly interface enable researchers to explore the potential proteasomal regulator landscape, generating new hypotheses to advance proteasome biology. This resource is set to facilitate the discovery of novel therapeutic targets, enhancing our approach to treating diseases such as neurodegenerative disorders and cancer. [ABSTRACT FROM AUTHOR]

We focused on exploring the diversity of viruses in the Napahai plateau wetland, a unique ecosystem located in Yunnan, China. While viruses in marine environments have been extensively studied for their influence on microbial metabolism and biogeochemical cycles, little is known about their composition and function in plateau wetlands. Metagenomic analysis was employed to investigate the viral diversity and biogeochemical impacts in the Napahai wetland. It revealed that the Caudoviricetes and Malgrandaviricetes class level was the most abundant viral category based on phylogenetic analysis. Additionally, a gene-sharing network highlighted the presence of numerous unexplored viruses and demonstrated their unique characteristics and significant variation within the viral community of the Napahai wetland. Furthermore, the study identified the auxiliary metabolic genes (AMGs). AMGs provide phages with additional functions, such as protection against host degradation and involvement in metabolic pathways, such as the pentose phosphate pathway and DNA biosynthesis. The viruses in the Napahai wetland were found to influence carbon, nitrogen, sulfur, and amino acid metabolism, indirectly contributing to biogeochemical cycling through these AMGs. Overall, the research sheds light on the diverse and unique viral communities in the Napahai plateau wetland and emphasizes the significant roles of viruses in microbial ecology. The findings contribute to a deeper understanding of the characteristics and ecological functions of viral communities in plateau wetland ecosystems. [ABSTRACT FROM AUTHOR]

All viruses are obligate intracellular parasites that use host machinery to synthesize viral proteins. In infected eukaryotes, viral secreted and transmembrane proteins are synthesized at the endoplasmic reticulum (ER). Many viruses refashion ER membranes into bespoke factories where viral products accumulate while evading host pattern recognition receptors. ER processes are tightly regulated to maintain cellular homeostasis, so viruses must either conform to ER regulatory mechanisms or subvert them to ensure efficient viral replication. Reticulophagy is a catabolic process that directs lysosomal degradation of ER components. There is accumulating evidence that reticulophagy serves as a form of antiviral defense; we call this defense “xERophagy” to acknowledge its relationship to xenophagy, the catabolic degradation of microorganisms by macroautophagy/autophagy. In turn, viruses can subvert reticulophagy to suppress host antiviral responses and support efficient viral replication. Here, we review the evidence for functional interplay between viruses and the host reticulophagy machinery.Abbreviations: AMFR: autocrine motility factor receptor; ARF4: ADP-ribosylation factor 4; ARL6IP1: ADP-ribosylation factor-like 6 interacting protein 1; ATL3: atlastin GTPase 3; ATF4: activating transcription factor 4; ATF6: activating transcription factor 6; BPIFB3: BPI fold containing family B, member 3; CALCOCO1: calcium binding and coiled coil domain 1; CAMK2B: calcium/calmodulin-dependent protein kinase II, beta; CANX: calnexin; CDV: canine distemper virus; CCPG1: cell cycle progression 1; CDK5RAP3/C53: CDK5 regulatory subunit associated protein 3; CIR: cargo-interacting region; CoV: coronavirus; CSNK2/CK2: casein kinase 2; CVB3: coxsackievirus B3; DAPK1: death associated protein kinase 1; DENV: dengue virus; DMV: double-membrane vesicles; EBOV: Ebola virus; EBV: Epstein-Barr Virus; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; EMCV: encephalomyocarditis virus; EMV: extracellular microvesicle; ER: endoplasmic reticulum; ERAD: ER-associated degradation; ERN1/IRE1: endoplasmic reticulum to nucleus signalling 1; EV: extracellular vesicle; EV71: enterovirus 71; FIR: RB1CC1/FIP200-interacting region; FMDV: foot-and-mouth disease virus; HCMV: human cytomegalovirus; HCV: hepatitis C virus; HMGB1: high mobility group box 1; HSPA5/BiP: heat shock protein 5; IFN: interferon; IFNG/IFN-γ: interferon gamma; KSHV: Kaposi’s sarcoma-associated herpesvirus; LIR: MAP1LC3/LC3-interacting region; LNP: lunapark, ER junction formation factor; MAP1LC3: microtubule-associated protein 1 light chain 3; MAP3K5/ASK1: mitogen-activated protein kinase kinase kinase 5; MAPK/JNK: mitogen-activated protein kinase; MeV: measles virus; MHV: murine hepatitis virus; NS: non-structural; PDIA3: protein disulfide isomerase associated 3; PRR: pattern recognition receptor; PRRSV: porcine reproductive and respiratory syndrome virus; RB1CC1/FIP200: RB1-inducible coiled-coil 1; RETREG1/FAM134B: reticulophagy regulator 1; RHD: reticulon homology domain; RTN3: reticulon 3; RTN3L: reticulon 3 long; sAIMs: shuffled Atg8-interacting motifs; SARS-CoV: severe acute respiratory syndrome coronavirus; SINV: Sindbis virus; STING1: stimulator of interferon response cGAMP interactor 1; SVV: Seneca Valley virus; SV40: simian virus 40; TEX264: testis expressed gene 264 ER-phagy receptor; TFEB: transcription factor EB; TRAF2: TNF receptor-associated factor 2; UIM: ubiquitin-interacting motif; UFM1: ubiquitin-fold modifier 1; UPR: unfolded protein response; VAPA: vesicle-associated membrane protein, associated protein A; VAPB: vesicle-associated membrane protein, associated protein B and C; VZV: varicella zoster virus; WNV: West Nile virus; XBP1: X-box binding protein 1; XBP1s: XBP1 spliced; xERophagy: xenophagy involving reticulophagy; ZIKV: Zika virus [ABSTRACT FROM AUTHOR]

A study published in Acta Neuropathologica explores the use of targeted whole-viral genome sequencing from formalin-fixed paraffin-embedded (FFPE) neuropathology specimens. The researchers conducted a proof-of-concept study using a viral nucleic acid enrichment protocol on 23 FFPE samples with confirmed viral infections. They found that the viral enrichment panel led to a significant enrichment of viral sequences, resulting in a high genome coverage and improved detection of viral integration sites. The study demonstrates that metagenomic sequencing of virus-enriched libraries from FFPE specimens is a valuable method for viral whole-genome sequencing, even in low-quality and low-biomass samples. [Extracted from the article]

The mucosa of the oral cavity is exposed to a large number of different microorganisms such as archaea, bacteria, fungi, parasites, and viruses. Among those, viruses cause specific infections, which can easily be transmitted from one person to another. The infectious route may not only include patients and their relatives but also the dental professional team. Thus, a wide knowledge regarding specific viral infections is crucial for the daily routine. Signs and symptoms of oral viral infections can be completely absent or develop into a pronounced clinical picture, so that early detection and information determine the further course of the infection and its influence on other inflammatory diseases, such as periodontitis, as well as the safety of family members and the social environment. As the clinical manifestation of viral infections may be highly variable leading to heterogenous mucosal lesions it is, in most cases, mandatory to differentiate them by specific microbiological tests in addition to clinical examination procedures. This article will give an overview of the role of viruses infecting the oral mucosa, and in addition, describe their clinical manifestation and management. [ABSTRACT FROM AUTHOR]

Monkeypox is a disease that, while less deadly and contagious than COVID-19, could pose a global pandemic threat. In the field of medical imaging, deep learning techniques offer promising results in the diagnosis of diseases. This study develops deep learning models using skin lesion images for early diagnosis of monkeypox. The research is divided into two key sections. In the first section, a deep learning model is developed using the Monkeypox Skin Image Dataset (MSID). The second section focuses on a model trained on a combined dataset, which merges the Monkeypox Skin Image, Monkeypox Master, and Monkeypox Original Image Datasets, referred to as HYBRID. The MSID dataset comprises 806 Monkeypox and 690 Non-Monkeypox images for training, along with 309 Monkeypox and 292 Non-Monkeypox images for testing, resulting in a total of 2,097 images of skin lesions with and without monkeypox. The HYBRID dataset includes 1,088 Monkeypox and 1,896 Non-Monkeypox images for training, as well as 468 Monkeypox and 812 Non-Monkeypox images for testing, resulting in a total of 4,264 skin lesion images. Five distinct deep learning models--DenseNet201, InceptionResNetV2, InceptionV3, NASNetLarge, and Xception--were applied to both datasets, and the outcomes were compared. The DenseNet201 model, when trained on augmented data, demonstrated remarkable performance in detecting monkeypox, achieving accuracy rates of 99.33% on the MSID dataset and 98.52% on the HYBRID dataset. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) is a methylation modification on the 6th nitrogen atom of the RNA molecule adenine, and is the most common post-transcriptional modification in messenger RNA (mRNA) and non-coding RNA (ncRNA). m6 modification plays a crucial role in all stage of RNA cycle, including RNA stabilization, splicing, nuclear export, folding, translation and degradation. m6A modification requires the participation of methyltransferase (writers), demethylase (erasers) and m6A readers. The important roles of m6A modification involved in virus-host interactions have been largely explored based on the rapid development of high-throughput RNA sequencing technology. Studies have shown that m6A modification participates in a variety of viral RNAs, and is associated with viral entrance, replication and progeny virion release. Viruses can also alter host transcriptome by m6A modification to impact viral infectivity or host resistance. This review explored the role of m6A modification in respiratory virus, retrovirus and herpes virus, etc. infected cells, and the regulatory effects of m6 modifications on viral replication and host immune response. It will help to further clarify the mechanisms of virus-host interactions and benefit the development of antiviral drugs. [ABSTRACT FROM AUTHOR]

The article discusses the association between airway bacterial colonization and bronchial remodeling in severe preschool wheezers. Pathogenic bacteria like NTHi, Moraxella catarrhalis, and Streptococcus pneumoniae are linked to wheezing, exacerbations, and hospitalizations in preschoolers. The presence of these bacteria is associated with neutrophilic inflammation and bronchial remodeling, particularly increased bronchial smooth muscle mass. Atopy and NTHi colonization independently influence bronchial smooth muscle mass and exacerbations in preschool wheezers, highlighting the complex interplay between bacterial colonization, atopy, and airway remodeling in severe wheezing. [Extracted from the article]

Simple Summary: Progress in passion fruit virus research has identified infections caused by Potyvirus, Begomovirus and other viruses, as well as genome sequences of major viruses such as PaVY, TeMV and BYMV, using molecular biology techniques. The transmission, infection cycle, and pathogenesis of these viruses have been elucidated. Virus control strategies include the use of resistant species, RNA interference, physical barriers, and chemotherapy. The focus of this review is on the impact of viruses on fruit quality, the importance of control measures for yield and quality, and the development of more effective prevention and control strategies. Passiflora edulis, also known as passion fruit, is celebrated for its rich nutritional content, distinctive flavour, and significant medicinal benefits. At present, viral diseases pose a major challenge to the passion fruit industry, affecting both the production and quality of the fruit. These diseases impede the sustainable and healthy growth of the passion fruit sector. In recent years, with the expansion of P. edulis cultivation areas, virus mutations, and advances in virus detection technology, an increasing number of virus species infecting P. edulis have been discovered. To date, more than 40 different virus species have been identified; however, there are different strains within the same virus. This poses a challenge for the control and prevention of P. edulis virus disease. Therefore, this review discusses the different types of viruses and their characteristics, modes of transmission, and effects on the growth of the passion fruit plant, as well as the mechanisms of virus generation and preventive measures, with the hope that these discussions will provide a comprehensive understanding of and countermeasures for viruses in passion fruit. [ABSTRACT FROM AUTHOR]

Commercially cultivated Prunus species are commonly grown in adjacent or mixed orchards and can be infected with unique or commonly shared viruses. Apple (Malus domestica), another member of the Rosacea and distantly related to Prunus, can share the same growing regions and common pathogens. Pollen can be a major route for virus transmission, and analysis of the pollen virome in tree fruit orchards can provide insights into these virus pathogen complexes from mixed production sites. Commercial honey bee (Apis mellifera) pollination is essential for improved fruit sets and yields in tree fruit production systems. To better understand the pollen-associated virome in tree fruits, metagenomics-based detection of plant viruses was employed on bee and pollen samples collected at four time points during the peak bloom period of apricot, cherry, peach, and apple trees at one orchard site. Twenty-one unique viruses were detected in samples collected during tree fruit blooms, including prune dwarf virus (PDV) and prunus necrotic ringspot virus (PNRSV) (Genus Ilarvirus, family Bromoviridae), Secoviridae family members tomato ringspot virus (genus Nepovirus), tobacco ringspot virus (genus Nepovirus), prunus virus F (genus Fabavirus), and Betaflexiviridae family member cherry virus A (CVA; genus Capillovirus). Viruses were also identified in composite leaf and flower samples to compare the pollen virome with the virome associated with vegetative tissues. At all four time points, a greater diversity of viruses was detected in the bee and pollen samples. Finally, the nucleotide sequence diversity of the coat protein regions of CVA, PDV, and PNRSV was profiled from this site, demonstrating a wide range of sequence diversity in pollen samples from this site. These results demonstrate the benefits of area-wide monitoring through bee pollination activities and provide new insights into the diversity of viruses in tree fruit pollination ecosystems. [ABSTRACT FROM AUTHOR]

Patients with hematological malignancies (HMs) are at high risk of respiratory viral infections due to the intrinsic deterioration of the immune system and chemotherapy treatments. In the recent past, SARS-CoV-2 respiratory viral infection has been responsible for most infectious complications in HMs. We analyzed 2950 samples from 505 patients admitted to the Hematology department from 2019 to 2023. The aim of this study was to determine the epidemiological trend of respiratory viruses in the SARS-CoV-2 era, the characteristics of the patients involved and their outcomes. In our analysis, we found a reduction in non-SARS-CoV-2 respiratory viral (NSRV) positivity during the pandemic period, although these data did not show statistical significance. Most of the HMs involved were Multiple Myeloma and Acute Myeloid Leukemia. Overall mortality rate was very low and characterized by the progression of the HMs as well as the worsening of respiratory failure. In conclusion, a reduction in non-COVID viral infections was highlighted, probably also thanks to the increase in prevention measures and environmental modifications of the viral background. [ABSTRACT FROM AUTHOR]