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Amsacta moorei entomopoxvirus (AMEV) is a poxvirus exclusively infecting insects and has been considered as a potential biological control agent. AMEV includes a CPD photolyase (AMV025, AMEV photolyase gene) responsible for converting cyclobutane pyrimidine dimers (CPDs) back into monomers. The codon usage patterns and their influence on the evolution of the AMEV photolyase gene are still widely uninvestigated. Here, we conducted a thorough examination of the codon usage bias (CUB) within the photolyase gene of AMEV and contrasted it with that of the photolyase genes found in five other entomopoxvirus species. Both nucleotide content and relative synonymous codon usage (RSCU) analysis indicated a higher frequency of AT-ending codons in the photolyase gene of AMEV. The effective number of codons (ENC) analysis revealed a high CUB in AMEV photolyase gene. The ENC-GC3s plot, neutrality plot, parity rule 2, correspondence analysis, and correlation analysis collectively indicated that both natural selection and mutation pressure impact the codon usage patterns of the AMEV photolyase gene, with natural selection emerging as the dominant factor shaping these patterns. Our research represents the inaugural effort to assess the codon usage pattern of the photolyase gene in AMEV, aiming to enhance our comprehension of the evolutionary dynamics within an entomopoxvirus. [ABSTRACT FROM AUTHOR]

As the world still vividly recalls the previous monkeypox (mpox) outbreak that impacted over 120 countries worldwide with more than 99,000 cases in 2022, we are now facing a second wave of infections from the monkeypox virus (MPXV), characterized by an exponential increase in cases. The current 2024 outbreak has already recorded more than 20,000 cases in Africa, marking a dramatic escalation compared to previous outbreaks. The predominance of the newly identified clade Ib variant, first detected in the Democratic Republic of the Congo (DRC) and now identified across multiple African nations and beyond, underscores its enhanced transmissibility and potential for international spread, evidenced by cases in Sweden and Thailand. The World Health Organization (WHO) declared on August 14, 2024, the current mpox outbreak a Public Health Emergency of International Concern (PHEIC), calling for heightened global public health measures. The ongoing pattern of unusual, frequent, and extensive outbreaks of mpox with potential global implications poses significant questions. This review addresses, in the format of 50 questions and answers, the 2024 mpox outbreak, detailing its characteristics, epidemiological data, and impact compared to previous outbreaks. It comprehensively explores critical questions related to MPXV virological characteristics, immunological response, clinical manifestations, epidemiology, diagnostics, and available treatments. The review also documents the significant and evolving challenges posed by the current mpox outbreak, highlighting its scale, spread, and public health response. [ABSTRACT FROM AUTHOR]

Phylogenetic analysis based on whole-genome sequences is the gold standard for monkeypox virus (MPXV) phylogeny. However, genomic epidemiology capability and capacity are lacking or limited in resource poor countries of sub-Saharan Africa. Therefore, these make real-time genome surveillance of MPXV virtually impossible. We hypothesized that phylogenetic analysis based on single, conserved genes will produce phylogenetic tree topology consistent with MPXV whole-genome phylogeny, thus serving as a reliable proxy to phylogenomic analysis. In this study, we analyzed 62 conserved MPXV genes and showed that Bayesian phylogenetic analysis based on five genes (OPG 066/E4L, OPG068/E6R, OPG079/I3L, OPG145/A18R, and OPG150/A23R) generated phylogenetic trees with 72.2–96.3% topology similarity index to the reference phylogenomic tree topology. Our results showed that phylogenetic analysis of the identified five genes singly or in combination can serve as surrogate for whole-genome phylogenetic analysis, and thus obviates the need for whole-genome sequencing and phylogenomic analysis in regions where genomic epidemiology competence and capacity are lacking or unavailable. This study is relevant to evolution and genome surveillance of MPXV in resource limited countries. [ABSTRACT FROM AUTHOR]

Myxoma virus (MYXV) is a double-stranded DNA-containing virus of the family Poxviridae, genus Leporipoxvirus. MYXV is an important model virus for evolutionary and immunological research and a promising oncolytic. In this study, we sequenced and analyzed two complete genomes of MYXV virus vaccine strains B-82 and Rabbivac-B, which are widely used for vaccine production in Russia. Here, we first show that MYXV vaccine strains B-82 and Rabbivac-B share a common origin with the American recombinant MYXV MAV vaccine strain. In addition, our data suggest that the MYXV B-82 and Rabbivac-B strains contain a number of genes at the 5′ and 3′ ends that are identical to the virulent MYXV Lausanne strain. Several unique genetic signatures were identified in the M013L, M017L, M023, and M121R genes, helping to achieve high genetic resolution between vaccine strains. Overall, these findings highlight the evolutionary flexibility of certain genes in the MYXV genome and provide insights into the molecular epidemiology of the virus and subsequent vaccine development. [ABSTRACT FROM AUTHOR]

The Africa Centers for Disease Control and Prevention declared mpox a Public Health Emergency of Continental Security (PHECS) in Africa. African public health systems have moved to mobilize a response against a backdrop of inherent significant challenges. With this commentary, we discuss how lessons from past public health emergencies, particularly COVID-19 and Ebola outbreaks, have prepared the region for improved disease surveillance, rapid response strategies, and effective public health communication and how these lessons can be applied to the mpox response, emphasizing the importance of strong healthcare infrastructure, effective data sharing, community engagement, targeted interventions, and robust contact tracing. Additionally, addressing misinformation and building public trust are crucial for controlling the spread of any disease. By leveraging these strategies, African countries can enhance their response to mpox. This includes improving diagnostic capabilities, strengthening cross-border collaborations, and prioritizing vaccination campaigns where needed. Ultimately, by applying the hard-earned lessons from the COVID-19 pandemic and Ebola outbreak, the East Africa region can better address the challenges posed by mpox and safeguard public health. [ABSTRACT FROM AUTHOR]

In eukaryotic cells, the endoplasmic reticulum is particularly important in post-translational modification of proteins before they are released extracellularly or sent to another endomembrane system. The correct three-dimensional folding of most proteins occurs in the ER lumen, which has an oxidative environment that is essential for the formation of disulfide bridges, which are important in maintaining protein structure. The ER is a versatile organelle that ensures the correct structure of proteins and is essential in the synthesis of lipids and sterols, in addition to offering support in the maintenance of intracellular calcium. Consequently, the cells needed to respond to demands caused by physiological conditions and pathological disturbances in the organelle homeostasis, leading to proper functioning of the cell or even programmed cell death. Disturbances to the ER function trigger a response to the accumulation of unfolded or misfolded proteins, known as the unfolded protein response. Such disturbances include abiotic stress, pharmacological agents, and intracellular pathogens, such as viruses. When misfolded proteins accumulate in the ER, they can undergo ubiquitination and proteasomal degradation through components of the ER-associated degradation system. Once a prolonged activity of the UPR pathway occurs, indicating that homeostasis cannot be reestablished, components of this pathway induce cell death by apoptosis. Here, we discuss how viruses have evolved ways to counteract UPR responses to maximize replication. This evolutionary viral ability is important to understand cell pathology and should be taken into account when designing therapeutic interventions and vaccines. [ABSTRACT FROM AUTHOR]

Parasitoid wasps are one of the most species‐rich groups of animals on Earth, due to their ability to successfully develop as parasites of nearly all types of insects. Unlike most known parasitoid wasps that specialize towards one or a few host species, Diachasmimorpha longicaudata is a generalist that can survive within multiple genera of tephritid fruit fly hosts, including many globally important pest species. Diachasmimorpha longicaudata has therefore been widely released to suppress pest populations as part of biological control efforts in tropical and subtropical agricultural ecosystems. In this study, we investigated the role of a mutualistic poxvirus in shaping the host range of D. longicaudata across three genera of agricultural pest species: two of which are permissive hosts for D. longicaudata parasitism and one that is a nonpermissive host. We found that permissive hosts Ceratitis capitata and Bactrocera dorsalis were highly susceptible to manual virus injection, displaying rapid virus replication and abundant fly mortality. However, the nonpermissive host Zeugodacus cucurbitae largely overcame virus infection, exhibiting substantially lower mortality and no virus replication. Investigation of transcriptional dynamics during virus infection demonstrated hindered viral gene expression and limited changes in fly gene expression within the nonpermissive host compared with the permissive species, indicating that the host range of the viral symbiont may influence the host range of D. longicaudata wasps. These findings also reveal that viral symbiont activity may be a major contributor to the success of D. longicaudata as a generalist parasitoid species and a globally successful biological control agent. [ABSTRACT FROM AUTHOR]

Background: Two outbreaks of swinepox were investigated in free-range domestic pig farms located in the northeastern side of Sicily, Italy. The disease is generally self-limiting with a low mortality rate, but morbidity can reach high rates in case of poor sanitary conditions, improper husbandry practices and ectoparasitic infestation. The presented cases are the first ever reported on the island and part of the few cases reported in domestic pigs. Case presentation: Carcasses condemned at the slaughterhouse and deceased pigs from Farm A and Farm B respectively, were referred for post-mortem examination and further investigations, with a strong suspect of SwinePox virus (SWPV) infection. Twelve deceased pigs were examined in total, showing poor body condition and pustular lesions scattered all over the cutaneous surfaces. Moreover, pigs from Farm B showed ocular lesions classified from Grade I to IV (from mild conjunctivitis to severe keratoconjunctivitis with corneal oedema, opacity, and ulcers). Final diagnosis was pursued by the microscopic assessment of skin lesions in both farms, which revealed the typical SWPV-lesion appearance, such as severe and disseminated ulcerative dermatitis and suspected inclusion bodies multifocally observed in the epidermis. Moreover, negative staining Electron Microscopy (nsEM) was performed on skin lesions and ocular swabs from Farm B, revealing in two samples the presence of brick-shaped viral particles, 220 nm long and 160 nm wide, with irregularly arranged surface tubules, identified as SWPV. The gene encoding the 482-bp fragment of the virus late transcription factor–3 was detected by PCR and sequencing revealed 99.79% identity and 100% query-cover with a strain previously isolated in Germany. Field clinical assessment was then performed in Farm B, revealing high overcrowding, poor sanitary conditions and improper husbandry practices, which are relevant risk factors for SWPV transmission. Conclusions: The present is the first case report of SWPV in free-range pigs raised in Sicily, an island of the Southern coast of Italy, and wants to raise awareness on a neglected disease, and cause of animal health and welfare issues. [ABSTRACT FROM AUTHOR]

Microtubule (MT)-dependent transport is a critical means of intracellular movement of cellular cargo by kinesin and dynein motors. MT-dependent transport is tightly regulated by cellular MT-associated proteins (MAPs) that directly bind to MTs and either promote or impede motor protein function. Viruses have been widely shown to usurp MT-dependent transport to facilitate their virion movement to sites of replication and/or for exit from the cell. However, it is unclear if viruses also negatively regulate MT-dependent transport. Using single-molecule motility and cellular transport assays, we show that the vaccinia virus (VV)-encoded MAP, A51R, inhibits kinesin-1-dependent transport along MTs in vitro and in cells. This inhibition is selective as the function of kinesin-3 is largely unaffected by VV A51R. Interestingly, we show that A51R promotes the perinuclear accumulation of cellular cargo transported by kinesin-1 such as lysosomes and mitochondria during infection. Moreover, A51R also regulates the release of specialized VV virions that exit the cell using kinesin-1-dependent movement. Using a fluorescently tagged rigor mutant of kinesin-1, we show that these motors accumulate on A51R-stabilized MTs, suggesting these stabilized MTs may form a "kinesin-1 sink" to regulate MT-dependent transport in the cell. Collectively, our findings uncover a new mechanism by which viruses regulate host cytoskeletal processes. [ABSTRACT FROM AUTHOR]

Mpox (monkeypox) is a neglected tropical disease that has received increased attention since the multi-nation outbreak that began in 2022. The virus is endemic in West and Central Africa, where the Democratic Republic of the Congo (DRC) is the most affected country. Clade I monkeypox virus (MPXV) infection is endemic in the DRC and has an overall case fatality rate of 10.6% among children and adults. A study conducted in Sankuru Province, DRC, from 2007 to 2011 demonstrated that 75% of pregnant women with mpox had miscarriages or stillbirth. Further analysis of a stillborn fetus showed that MPXV could infect both the placenta and fetus, causing congenital infection. No additional cases of Clade I MPXV in pregnant women were reported until a new outbreak occurred in South Kivu Province during 2023 and 2024. Eight pregnant women having Clade I MPXV infection were identified, of whom four had either miscarriages or stillbirth, representing a 50% fetal mortality rate. These reports confirm previous data from the DRC that indicate the capability of Clade I MPXV to affect the fetus, causing congenital infection and fetal loss in a high percentage of cases. In this article, we review both past and new data from the DRC on the effects of Clade I MPXV during pregnancy and discuss the association of mpox with fetal loss. [ABSTRACT FROM AUTHOR]

Background and Aims: A double‐stranded DNA virus called monkeypox virus (MPV) belonging to the Poxviridae family and Orthopoxvirus genus causes monkeypox (mpox) infection. This virus used to infect only Central, East, and West Africa. However, it has spread to an extent outside Africa recently. The range of MPV outbreaks was so high that on July 23, 2022, the World Health Organization (WHO) declared it a Public Health Emergency of International Concern (PHEIC). About a year later, the WHO notified the end of a global public health emergency for mpox on May 11, 2023. Here, we aimed to assess the current pathogenicity and potential risk of MPV causing public health emergencies. Methods: We searched information from published articles available in PubMed, Scopus, and ScienceDirect. We used monkeypox, mpox, monkeypox outbreak, and monkeypox virus as keywords during the literature search. Results: Many new variants of MPV have emerged throughout the world that created PHEIC for mpox. Considering the low lethality and transmission rate, mpox is no longer a global public health threat. In addition, the availability of therapeutic and preventive measures helped the healthcare authorities fight the mpox infection in an efficient manner. In this review, we have portrayed the history and evolution of mpox from past to present and an idea of its future outcomes. Also, we have discussed the symptoms related to mpox and approved antiviral treatment strategies to fight off the infection in this piece. This review also emphasized the preventive guidelines set by the WHO for patients, caregivers, and healthcare providers to control the outbreak of mpox infection. Conclusion: We believe this article would give an idea about the potential public health threats of the recent multi‐country monkeypox outbreak to the healthcare authorities for taking measures accordingly. [ABSTRACT FROM AUTHOR]

Viral vector vaccines represent a substantial advancement in immunization technology, offering numerous benefits over traditional vaccine modalities. The Orf virus (ORFV) strain D1701-VrV is a particularly promising candidate for vaccine development due to its distinctive attributes, such as a good safety profile, the ability to elicit both humoral and cellular immunity, and its favorable genetic and thermal stability. Despite ORFV's theoretical safety advantages, such as its narrow host range and limited systemic spread post-inoculation, a critical gap persists between these theoretical benefits and the empirical evidence regarding its in vivo safety profile. This discrepancy underscores the need for comprehensive preclinical validations to bridge this knowledge gap, especially considering ORFV's use in humans. Our research introduces Prime-2-CoV, an innovative ORFV-based vaccine candidate against COVID-19, designed to elicit a robust immune response by expressing SARS-CoV-2 Nucleocapsid and Spike proteins. Currently under clinical trials, Prime-2-CoV marks the inaugural application of ORFV in human subjects. Addressing the aforementioned safety concerns, our extensive preclinical evaluation, including an environmental risk assessment (ERA) and detailed pharmacokinetic studies in rats and immunocompromised NOG mice, demonstrates Prime-2-CoV's favorable pharmacokinetic profile, negligible environmental impact, and minimal ERA risks. These findings not only affirm the vaccine's safety and efficacy but also pioneer the use of ORFV-based therapeutics, highlighting its potential for wider therapeutic applications. [ABSTRACT FROM AUTHOR]

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In 2022, a series of human monkeypox cases in multiple countries led to the largest and most widespread outbreak outside the known endemic areas. Setup of proper genomic surveillance is of utmost importance to control such outbreaks. To this end, we performed Nanopore (PromethION P24) and Illumina (NextSeq. 2000) Whole Genome Sequencing (WGS) of a monkeypox sample. Adaptive sampling was applied for in silico depletion of the human host genome, allowing for the enrichment of low abundance viral DNA without a priori knowledge of sample composition. Nanopore sequencing allowed for high viral genome coverage, tracking of sample composition during sequencing, strain determination, and preliminary assessment of mutational pattern. In addition to that, only Nanopore data allowed us to resolve the entire monkeypox virus genome, with respect to two structural variants belonging to the genes OPG015 and OPG208. These SVs in important host range genes seem stable throughout the outbreak and are frequently misassembled and/or misannotated due to the prevalence of short read sequencing or short read first assembly. Ideally, standalone standard Illumina sequencing should not be used for Monkeypox WGS and de novo assembly, since it will obfuscate the structure of the genome, which has an impact on the quality and completeness of the genomes deposited in public databases and thus possibly on the ability to evaluate the complete genetic reason for the host range change of monkeypox in the current pandemic. [ABSTRACT FROM AUTHOR]

The skin is a complex tissue that provides a strong physical barrier against invading pathogens. Despite this, many viruses can access the skin and successfully replicate in either the epidermal keratinocytes or dermal immune cells. In this review, we provide an overview of the antiviral T cell biology responding to cutaneous viral infections and how these responses differ depending on the cellular targets of infection. Much of our mechanistic understanding of T cell surveillance of cutaneous infection has been gained from murine models of poxvirus and herpesvirus infection. However, we also discuss other viral infections, including flaviviruses and papillomaviruses, in which the cutaneous T cell response has been less extensively studied. In addition to the mechanisms of successful T cell control of cutaneous viral infection, we highlight knowledge gaps and future directions with possible impact on human health. [ABSTRACT FROM AUTHOR]

Modified vaccinia virus Ankara (MVA) has been widely tested in clinical trials as recombinant vector vaccine against infectious diseases and cancers in humans and animals. However, one biosafety concern about the use of MVA vectored vaccine is the potential forMVA to recombinewith naturally occurring orthopoxviruses in cells and hosts in which itmultiplies poorly and, therefore, producing viruses with mosaic genomes with altered genetic and phenotypic properties. We previously conducted co-infection and superinfection experiments with MVA vectored influenza vaccine (MVA-HANP) and a feline Cowpox virus (CPXV-No-F1) in Vero cells (that were semipermissive to MVA infection) and showed that recombination occurred in both coinfected and superinfected cells. In this study, we selected the putative recombinant viruses and performed genomic characterization of these viruses. Some putative recombinant viruses displayed plaque morphology distinct of that of the parental viruses. Our analysis demonstrated that they had mosaic genomes of different lengths. The recombinant viruses, with a genome more similar to MVA-HANP (>50%), rescued deleted and/or fragmented genes in MVA and gained new host ranges genes. Our analysis also revealed that someMVA-HANP contained a partially deleted transgene expression cassette and one recombinant virus contained part of the transgene expression cassette similar to that incomplete MVA-HANP. The recombination in co-infected and superinfected Vero cells resulted in recombinant viruses with unpredictable biological and genetic properties as well as recovery of delete/fragmented genes in MVA and transfer of the transgene into replication competent CPXV. These results are relevant to hazard characterization and risk assessment of MVA vectored biologicals. [ABSTRACT FROM AUTHOR]

Poxviruses have evolved a wide array of mechanisms to evade the immune response, and we provide an overview of the different immunomodulatory strategies. Poxviruses prevent the recognition of viral DNA that triggers the immune responses and inhibit signaling pathways within the infected cell. A unique feature of poxviruses is the production of secreted proteins that mimic cytokines and cytokine receptors, acting as decoy receptors to neutralize the activity of cytokines and chemokines. The capacity of these proteins to evade cellular immune responses by inhibiting cytokine activation is complemented by poxviruses' strategies to block natural killer cells and cytotoxic T cells, often through interfering with antigen presentation pathways. Mechanisms that target complement activation are also encoded by poxviruses. Virus-encoded proteins that target immune molecules and pathways play a major role in immune modulation, and their contribution to viral pathogenesis, facilitating virus replication or preventing immunopathology, is discussed. [ABSTRACT FROM AUTHOR]

Vertical transmission has been described following monkeypox virus (MPXV) infection in pregnant women. The presence of MPXV has been reported in the placenta from infected women, but whether pathogens colonize placenta remains unexplored. We identify trophoblasts as a target cell for MPXV replication. In a pan‐microscopy approach, we decipher the specific infectious cycle of MPXV and inner cellular structures in trophoblasts. We identified the formation of a specialized region for viral morphogenesis and replication in placental cells. We also reported infection‐induced cellular remodeling. We found that MPXV stimulates cytoskeleton reorganization with intercellular extensions for MPXV cell spreading specifically to trophoblastic cells. Altogether, the specific infectious cycle of MPXV in trophoblast cells and these protrusions that were structurally and morphologically similar to filopodia reveal new insights into the infection of MPXV. [ABSTRACT FROM AUTHOR]

In this study, we demonstrated the antiviral efficacy of hesperetin against multiple poxviruses, including buffalopox virus (BPXV), vaccinia virus (VACV), and lumpy skin disease virus (LSDV). The time‐of‐addition and virus step‐specific assays indicated that hesperetin reduces the levels of viral DNA, mRNA, and proteins in the target cells. Further, by immunoprecipitation (IP) of the viral RNA from BPXV‐infected Vero cells and a cell‐free RNA‐IP assay, we demonstrated that hesperetin‐induced reduction in BPXV protein synthesis is also consistent with diminished interaction between eukaryotic translation initiation factor eIF4E and the 5′ cap of viral mRNA. Molecular docking and MD simulation studies were also consistent with the binding of hesperetin to the cap‐binding pocket of eIF4E, adopting a conformation similar to m7GTP binding. Furthermore, in a BPXV egg infection model, hesperetin was shown to suppress the development of pock lesions on the chorioallantoic membrane and associated mortality in the chicken embryos. Most importantly, long‐term culture of BPXV in the presence of hesperetin did not induce the generation of drug‐resistant viral mutants. In conclusion, we, for the first time, demonstrated the antiviral activity of hesperetin against multiple poxviruses, besides providing some insights into its potential mechanisms of action. [ABSTRACT FROM AUTHOR]

A juvenile grey‐headed flying fox (GHFF) (Pteropus poliocephalus) presented to the Australia Zoo Wildlife Hospital after a wildlife carer found the animal hanging on the outside of an aviary. On presentation, the animal was emaciated and moribund with disseminated, multifocal, depigmented and proliferative lesions on the wing membranes and skin of the neck. Histopathology revealed multiple, well‐circumscribed proliferative epidermal lesions with intracytoplasmic inclusion bodies. A poxvirus was identified via transmission electron microscopy and next‐generation sequencing (NGS). Analysis of sequences obtained demonstrated 99% nucleotide identity to Pteropox virus strain Australia (GenBank KU980965). To the authors' knowledge, this paper describes the first case of Pteropox virus infection in a GHFF. [ABSTRACT FROM AUTHOR]

The persistent epidemic of human mpox, caused by mpox virus (MPXV), raises concerns about the future spread of MPXV and other poxviruses. MPXV is a typical zoonotic virus which can infect human and cause smallpox-like symptoms. MPXV belongs to the Poxviridae family, which has a relatively broad host range from arthropods to vertebrates. Cross-species transmission of poxviruses among different hosts has been frequently reported and resulted in numerous epidemics. Poxviruses have a complex linear double-strand DNA genome that encodes hundreds of proteins. Genes related to the host range of poxvirus are called host range genes (HRGs). This review briefly introduces the taxonomy, phylogeny and hosts of poxviruses, and then comprehensively summarizes the current knowledge about the cross-species transmission of poxviruses. In particular, the HRGs of poxvirus are described and their impacts on viral host range are discussed in depth. We hope that this review will provide a comprehensive perspective about the current progress of researches on cross-species transmission and HRG variation of poxviruses, serving as a valuable reference for academic studies and disease control in the future. [ABSTRACT FROM AUTHOR]

Lumpy skin disease virus (LSDV) is a member of the capripoxvirus (CPPV) genus of the Poxviridae family. LSDV is a rapidly emerging, high-consequence pathogen of cattle, recently spreading from Africa and the Middle East into Europe and Asia. We have sequenced the whole genome of historical LSDV isolates from the Pirbright Institute virus archive, and field isolates from recent disease outbreaks in Sri Lanka, Mongolia, Nigeria and Ethiopia. These genome sequences were compared to published genomes and classified into different subgroups. Two subgroups contained vaccine or vaccine-like samples ("Neethling-like" clade 1.1 and "Kenya-like" subgroup, clade 1.2.2). One subgroup was associated with outbreaks of LSD in the Middle East/Europe (clade 1.2.1) and a previously unreported subgroup originated from cases of LSD in west and central Africa (clade 1.2.3). Isolates were also identified that contained a mix of genes from both wildtype and vaccine samples (vaccine-like recombinants, grouped in clade 2). Whole genome sequencing and analysis of LSDV strains isolated from different regions of Africa, Europe and Asia have provided new knowledge of the drivers of LSDV emergence, and will inform future disease control strategies. [ABSTRACT FROM AUTHOR]

Cellular attachment of viruses determines their cell tropism and species specificity. For entry, vaccinia, the prototypic poxvirus, relies on four binding proteins and an eleven-protein entry fusion complex. The contribution of the individual virus binding proteins to virion binding orientation and membrane fusion is unclear. Here, we show that virus binding proteins guide side-on virion binding and promote curvature of the host membrane towards the virus fusion machinery to facilitate fusion. Using a membrane-bleb model system together with super-resolution and electron microscopy we find that side-bound vaccinia virions induce membrane invagination in the presence of low pH. Repression or deletion of individual binding proteins reveals that three of four contribute to binding orientation, amongst which the chondroitin sulfate binding protein, D8, is required for host membrane bending. Consistent with low-pH dependent macropinocytic entry of vaccinia, loss of D8 prevents virion-associated macropinosome membrane bending, disrupts fusion pore formation and infection. Our results show that viral binding proteins are active participants in successful virus membrane fusion and illustrate the importance of virus protein architecture for successful infection. Synopsis: Poxvirus membranes are organized into distinct binding and fusion domains. To facilitate fusion, the virus binding protein D8 actively curves host membranes to promote their contact with the virus fusion machinery. Interactions between vaccinia D8 and host chondroitin sulfates drive low pH-dependent host membrane curvature. VACV proteins A26, D8 and H3 show hierarchical and compensatory contributions to virus binding affinity and orientation. VACV adapts cellular attachment factor usage depending on which viral binding proteins and cell factors are available. Membrane organization into functionally distinct domains maximizes virion binding and fusion efficiency for productive infection. Poxvirus membranes are organized into distinct binding and fusion domains. To facilitate fusion, the virus binding protein D8 actively curves host membranes to promote their contact with the virus fusion machinery. [ABSTRACT FROM AUTHOR]

A 2‐year‐old, domestic shorthair cat was presented to a referral hospital with a 4‐day history of inappetence and lethargy, which had progressed to dyspnoea and tachypnoea. Investigations performed included full haematology and biochemistry and computed tomography of the thorax. A large, heterogeneously contrast enhancing and poorly marginated mass lesion was noted in the left caudal lung lobe, along with areas of ground‐glass attenuation throughout the left lung field. Fine‐needle aspirates of the pulmonary mass revealed neutrophilic and macrophagic inflammation, with moderate numbers of mildly atypical epithelial cells. The cat was treated with broad‐spectrum antibiotics and returned with multifocal crusted cutaneous lesions 5 days later. Poxvirus polymerase chain reaction was performed on the skin lesion smears and subsequently on the pulmonary mass aspirates, both proving positive for poxvirus. Repeat computed tomography was performed 5 weeks later, revealing complete resolution of the pulmonary changes. [ABSTRACT FROM AUTHOR]

Myxoma virus (MYXV) is a Leporipoxvirus (genus) belonging to the family Poxviridae; it is characterised by a genome of approximately 161 kb dsDNA encoding for several proteins that play an essential role in both host spectrum determination and immunomodulation. The healthy reservoir of the virus is Sylvilagus spp. At the same time, in wild and domestic European rabbits (Oryctolagus cuniculus), MYXV is the etiologic agent of myxomatosis, a disease with an extremely high mortality rate. In 2014, an interspecies jump of MYXV was reported in Lepus europaeus in the UK. In 2018, myxomatosis induced by a new recombinant strain called MYXV-To was identified during a large outbreak in Iberian hares (Lepus granatensis) in Spain. Here, we describe the case of myxomatosis in another hare species: an adult male Italian hare (Lepus corsicanus) found dead in 2018 in Sicily with lesions suggestive of myxomatosis and treponema infection. Laboratory tests, e.g., end-point PCR and negative staining electron microscopy, confirmed the presence of both pathogens. MYXV was then isolated from tissue samples in permissive cells and sequenced using NGS technology. Main genomic differences concerning known MYXV strains are discussed. [ABSTRACT FROM AUTHOR]

Infection at barrier sites, e.g., skin, activates local immune defenses that limit pathogen spread, while preserving tissue integrity. Phenotypically distinct γδ T cell populations reside in skin, where they shape immunity to cutaneous infection prior to onset of an adaptive immune response by conventional αβ CD4+ (TCD4+) and CD8+ (TCD8+) T cells. To examine the mechanisms used by γδ T cells to control cutaneous virus replication and tissue pathology, we examined γδ T cells after infection with vaccinia virus (VACV). Resident γδ T cells expanded and combined with recruited γδ T cells to control pathology after VACV infection. However, γδ T cells did not play a role in control of local virus replication or blockade of systemic virus spread. We identified a unique wound healing signature that has features common to, but also features that antagonize, the sterile cutaneous wound healing response. Tissue repair generally occurs after clearance of a pathogen, but viral wound healing started prior to the peak of virus replication in the skin. γδ T cells contributed to wound healing through induction of multiple cytokines/growth factors required for efficient wound closure. Therefore, γδ T cells modulate the wound healing response following cutaneous virus infection, maintaining skin barrier function to prevent secondary bacterial infection. [ABSTRACT FROM AUTHOR]

The sudden emergence of SARS-CoV-2 demonstrates the need for new vaccines that rapidly protect in the case of an emergency. In this study, we developed a recombinant MVA vaccine co-expressing SARS-CoV-2 prefusion-stabilized spike protein (ST) and SARS-CoV-2 nucleoprotein (N, MVA-SARS-2-ST/N) as an approach to further improve vaccine-induced immunogenicity and efficacy. Single MVA-SARS-2-ST/N vaccination in K18-hACE2 mice induced robust protection against lethal respiratory SARS-CoV-2 challenge infection 28 days later. The protective outcome of MVA-SARS-2-ST/N vaccination correlated with the activation of SARS-CoV-2-neutralizing antibodies (nABs) and substantial amounts of SARS-CoV-2-specific T cells especially in the lung of MVA-SARS-2-ST/N-vaccinated mice. Emergency vaccination with MVA-SARS-2-ST/N just 2 days before lethal SARS-CoV-2 challenge infection resulted in a delayed onset of clinical disease outcome in these mice and increased titers of nAB or SARS-CoV-2-specific T cells in the spleen and lung. These data highlight the potential of a multivalent COVID-19 vaccine co-expressing S- and N-protein, which further contributes to the development of rapidly protective vaccination strategies against emerging pathogens. [ABSTRACT FROM AUTHOR]

Protein kinase R (PKR) is a double‐stranded RNA (dsRNA) binding protein that plays a crucial role in innate immunity during viral infection and can restrict both DNA and RNA viruses. The potency of its antiviral function is further reflected by the large number of viral‐encoded PKR antagonists. However, much about the regulation of dsRNA accumulation and PKR activation during viral infection remains unknown. Since DNA viruses do not have an RNA genome or RNA replication intermediates like RNA viruses do, PKR‐mediated dsRNA detection in the context of DNA virus infection is particularly intriguing. Here, we review the current state of knowledge regarding the regulation of PKR activation and its antagonism during infection with DNA viruses. [ABSTRACT FROM AUTHOR]

Vaccinia virus (Orthopoxvirus) F17 protein is a major virion structural phosphoprotein having a molecular weight of 11 kDa. Recently, it was shown that F17 synthesised in infected cells interacts with mTOR subunits to evade cell immunity and stimulate late viral protein synthesis. Several years back, we purified an 11 kDa protein that inhibited protein synthesis in reticulocyte lysate from virions, and that possesses all physico-chemical properties of F17 protein. To investigate this discrepancy, we used defective vaccinia virus particles devoid of the F17 protein (designated iF17− particles) to assess their ability to inhibit protein synthesis. To this aim, we purified iF17− particles from cells infected with a vaccinia virus mutant which expresses F17 only in the presence of IPTG. The SDS-PAGE protein profiles of iF17− particles or derived particles, obtained by solubilisation of the viral membrane, were similar to that of infectious iF17 particles. As expected, the profiles of full iF17− particles and those lacking the viral membrane were missing the 11 kDa F17 band. The iF17− particles did attach to cells and injected their viral DNA into the cytoplasm. Co-infection of the non-permissive BSC40 cells with a modified vaccinia Ankara (MVA) virus, expressing an mCherry protein, and iF17− particles, induced a strong mCherry fluorescence. Altogether, these experiments confirmed that the iF17− particles can inject their content into cells. We measured the rate of protein synthesis as a function of the multiplicity of infection (MOI), in the presence of puromycin as a label. We showed that iF17− particles did not inhibit protein synthesis at high MOI, by contrast to the infectious iF17 mutant. Furthermore, the measured efficiency to inhibit protein synthesis by the iF17 mutant virus generated in the presence of IPTG, was threefold to eightfold lower than that of the wild-type WR virus. The iF17 mutant contained about threefold less F17 protein than wild-type WR. Altogether these results strongly suggest that virion-associated F17 protein is essential to mediate a stoichiometric inhibition of protein synthesis, in contrast to the late synthesised F17. It is possible that this discrepancy is due to different phosphorylation states of the free and virion-associated F17 protein. [ABSTRACT FROM AUTHOR]

Copyright of Die Dermatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aging is associated with a decline in immune system functionality. So-called immunosenescence may impair the successful vaccination of elderly people. Thus, improved vaccination strategies also suitable for an aged immune system are required. Modified Vaccinia virus Ankara (MVA) is a highly attenuated and replication-deficient vaccinia virus that has been established as a multipurpose viral vector for vaccine development against various infections. We characterized a recombinant MVA expressing a prefusion-stabilized version of SARS-CoV-2 S protein (MVA-ST) in an aged-hamster model for COVID-19. Intramuscular MVA-ST immunization resulted in protection from disease and severe lung pathology. Importantly, this protection was correlated with a potent activation of SARS-CoV-2 specific T-cells and neutralizing antibodies. Our results suggest that MVA vector vaccines merit further evaluation in preclinical models to contribute to future clinical development as candidate vaccines in elderly people to overcome the limitations of age-dependent immunosenescence. [ABSTRACT FROM AUTHOR]

Copyright of Virologie is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The sporadic outbreaks of human mpox diseases in the nearly twenty years have seriously influenced the public health and economic. Though the reservoirs of mpox virus (MPXV) are mainly rodents, it could spill over to humans by direct contact and cause self-limiting infection with the symptom of lymphadenopathy and rash on the skin. Since the first case reported outside Africa in the USA at the beginning of this century in America, MPXV has been gradually prevalent globally and become an increasing public threat. With the advancing technology of viral detection and gene sequencing, many novel poxviruses were detected which enriched the variety of Poxviridae family. In this review, we provide a comprehensive overview on the latest classification, host spectrum, genome feature, pathogenicity and the evolution of MPXV and other poxviruses. This information will promote our understanding of the phylogenetic relationship and infectious transmission of pathogenic poxviruses and contribute to future viral researches and disease control. [ABSTRACT FROM AUTHOR]

Smallpox was a highly contagious disease caused by the variola virus. The disease affected millions of people over thousands of years and variola virus ranked as one of the deadliest viruses in human history. The complete eradication of smallpox in 1980, a major triumph in medicine, was achieved through a global vaccination campaign using a less virulent poxvirus, vaccinia virus. Despite this success, the herd immunity established by this campaign has significantly waned, and concerns are rising about the potential reintroduction of variola virus as a biological weapon or the emergence of zoonotic poxviruses. These fears were further fueled in 2022 by a global outbreak of monkeypox virus (mpox), which spread to over 100 countries, thereby boosting interest in developing new vaccines using molecular approaches. However, poxviruses are complex and creating modern vaccines against them is challenging. This review focuses on the structural biology of the six major neutralization determinants on poxviruses (D8, H3, A27, L1, B5, and A33), the localization of epitopes targeted by neutralizing antibodies, and their application in the development of subunit vaccines. [ABSTRACT FROM AUTHOR]

The 2022 global Mpox outbreak swiftly introduced unforeseen diversity in the monkeypox virus (MPXV) population, resulting in numerous Clade IIb sublineages. This propagation of new MPXV mutations warrants the thorough re-investigation of previously recommended or validated primers designed to target MPXV genomes. In this study, we explored 18 PCR primer sets and examined their binding specificity against 5210 MPXV genomes, representing all the established MPXV lineages. Our results indicated that only five primer sets resulted in almost all perfect matches against the targeted MPXV lineages, and the remaining primer sets all contained 1–2 mismatches against almost all the MPXV lineages. We further investigated the mismatched primer-genome pairs and discovered that some of the primers overlapped with poorly sequenced and assembled regions of the MPXV genomes, which are consistent across multiple lineages. However, we identified 173 99% genome-wide conserved regions across all 5210 MPXV genomes, representing 30 lineages/clades with at least 80% lineage-specific consensus for future primer development and primer binding evaluation. This exercise is crucial to ensure that the current detection schemes are robust and serve as a framework for primer evaluation in clinical testing development for other infectious diseases. [ABSTRACT FROM AUTHOR]

The aim of personalized cancer vaccines is to elicit potent and tumor-specific immune responses against neoantigens specific to each patient and to establish durable immunity, while minimizing the adverse events. Over recent years, there has been a renewed interest in personalized cancer vaccines, primarily due to the advancement of innovative technologies for the identification of neoantigens and novel vaccine delivery platforms. Here, we review the emerging field of personalized cancer vaccination, with a focus on the use of viral vectors as a vaccine platform. The recent advancements in viral vector technology have led to the development of efficient production processes, positioning personalized viral vaccines as one of the preferred technologies. Many clinical trials have shown the feasibility, safety, immunogenicity and, more recently, preliminary evidence of the anti-tumor activity of personalized vaccination, fostering active research in the field, including further clinical trials for different tumor types and in different clinical settings. [ABSTRACT FROM AUTHOR]

Oncolytic viruses (OVs) have emerged as one of the most promising cancer immunotherapy agents that selectively target and kill cancer cells while sparing normal cells. OVs are from diverse families of viruses and can possess either a DNA or an RNA genome. These viruses also have either a natural or engineered tropism for cancer cells. Oncolytic DNA viruses have the additional advantage of a stable genome and multiple-transgene insertion capability without compromising infection or replication. Herpes simplex virus 1 (HSV-1), a member of the oncolytic DNA viruses, has been approved for the treatment of cancers. This success with HSV-1 was achievable by introducing multiple genetic modifications within the virus to enhance cancer selectivity and reduce the toxicity to healthy cells. Here, we review the natural characteristics of and genetically engineered changes in selected DNA viruses that enhance the tumor tropism of these oncolytic viruses. [ABSTRACT FROM AUTHOR]

After recognition of cognate antigen (Ag), effector CD8+ T cells secrete serine proteases called granzymes in conjunction with perforin, allowing granzymes to enter and kill target cells. While the roles for some granzymes during antiviral immune responses are well characterized, the function of others, such as granzyme C and its human ortholog granzyme H, is still unclear. Granzyme C is constitutively expressed by mature, cytolytic innate lymphoid 1 cells (ILC1s). Whether other antiviral effector cells also produce granzyme C and whether it is continually expressed or responsive to the environment is unknown. To explore this, we analyzed granzyme C expression in different murine skin-resident antiviral lymphocytes. At steady-state, dendritic epidermal T cells (DETCs) expressed granzyme C while dermal γδ T cells did not. CD8+ tissue-resident memory T cells (TRM) generated in response to cutaneous viral infection with the poxvirus vaccinia virus (VACV) also expressed granzyme C. Both DETCs and virus-specific CD8+ TRM upregulated granzyme C upon local VACV infection. Continual Ag exposure was not required for maintained TRM expression of granzyme C, although re-encounter with cognate Ag boosted expression. Additionally, IL-15 treatment increased granzyme C expression in both DETCs and TRM. Together, our data demonstrate that granzyme C is widely expressed by antiviral T cells in the skin and that expression is responsive to both environmental stimuli and TCR engagement. These data suggest that granzyme C may have functions other than killing in tissue-resident lymphocytes. [ABSTRACT FROM AUTHOR]

Poxviruses belong to the Poxviridae family, a group of pathogens known for their high infectivity in humans, posing significant health threats. One of the most well‐known representatives of poxvirus infections is smallpox, which has been successfully eradicated. However, in recent years, there has been a resurgence in cases of mpox, another member of the Poxviridae family, raising concerns about the potential for a global pandemic or a worldwide health crisis. While the typical clinical presentation of mpox and other poxvirus infections often involves cutaneous lesions, there have been reports of various atypical and non‐classic clinical manifestations. Dermoscopy has emerged as a crucial diagnostic tool, aiding dermatologists in clinical practice to make informed decisions. In this summary, we provide an overview of the clinical and dermoscopic features of representative cutaneous lesions associated with human poxvirus infections, including mpox, orf, milker's nodule, and molluscum contagiosum. [ABSTRACT FROM AUTHOR]

Serine protease inhibitors, SERPINS, are a highly conserved family of proteins that regulate serine proteases in the central coagulation and immune pathways, representing 2–10% of circulating proteins in the blood. Serine proteases form cascades of sequentially activated enzymes that direct thrombosis (clot formation) and thrombolysis (clot dissolution), complement activation in immune responses and also programmed cell death (apoptosis). Virus-derived serpins have co-evolved with mammalian proteases and serpins, developing into highly effective inhibitors of mammalian proteolytic pathways. Through interacting with extracellular and intracellular serine and cysteine proteases, viral serpins provide a new class of highly active virus-derived coagulation-, immune-, and apoptosis-modulating drug candidates. Viral serpins have unique characteristics: (1) function at micrograms per kilogram doses; (2) selectivity in targeting sites of protease activation; (3) minimal side effects at active concentrations; and (4) the demonstrated capacity to be modified, or fine-tuned, for altered protease targeting. To date, the virus-derived serpin class of biologics has proven effective in a wide range of animal models and in one clinical trial in patients with unstable coronary disease. Here, we outline the known viral serpins and review prior studies with viral serpins, considering their potential for application as new sources for immune-, coagulation-, and apoptosis-modulating therapeutics. [ABSTRACT FROM AUTHOR]

Zoonotic poxviruses such as mpox virus (MPXV) continue to threaten public health safety since the eradication of smallpox. Vaccinia virus (VACV), the prototypic poxvirus used as the vaccine strain for smallpox eradication, is the best-characterized member of the poxvirus family. VACV encodes a serine protease inhibitor 1 (SPI-1) conserved in all orthopoxviruses, which has been recognized as a host range factor for modified VACV Ankara (MVA), an approved smallpox vaccine and a promising vaccine vector. FAM111A (family with sequence similarity 111 member A), a nuclear protein that regulates host DNA replication, was shown to restrict the replication of a VACV SPI-1 deletion mutant (VACV-ΔSPI-1) in human cells. Nevertheless, the detailed antiviral mechanisms of FAM111A were unresolved. Here, we show that FAM111A is a potent restriction factor for VACV-ΔSPI-1 and MVA. Deletion of FAM111A rescued the replication of MVA and VACV-ΔSPI-1 and overexpression of FAM111A significantly reduced viral DNA replication and virus titers but did not affect viral early gene expression. The antiviral effect of FAM111A necessitated its trypsin-like protease domain and DNA-binding domain but not the PCNA-interacting motif. We further identified that FAM111A translocated into the cytoplasm upon VACV infection by degrading the nuclear pore complex via its protease activity, interacted with VACV DNA-binding protein I3, and promoted I3 degradation through autophagy. Moreover, SPI-1 from VACV, MPXV, or lumpy skin disease virus was able to antagonize FAM111A by prohibiting its nuclear export. Our findings reveal the detailed mechanism by which FAM111A inhibits VACV and provide explanations for the immune evasive function of VACV SPI-1. [ABSTRACT FROM AUTHOR]

Mpox virus, a member of genus Orthopoxvirus, causes rash and flu‐like symptoms in humans. In the recent global outbreak, it was reported from several geographical areas that have not historically reported mpox. Point of care, sensitive and specific mpox diagnostic assays are critical in checking the spread of the disease. We have developed a clustered regularly interspaced short palindromic repeats associated Cas12a nuclease‐based assay for detecting mpox virus. Mpox specific conserved sequences were identified in polA (E9L) gene which differ by a single nucleotide polymorphism (SNP) from all the viruses present in the genus Orthopoxvirus. This SNP was exploited in our assay to specifically distinguish mpox virus from other related orthopox viruses with a limit of detection of 1 copy/μl in 30 min. The assay exhibits a sensitive and specific detection of mpox virus which can prove to be of practical value for its surveillance in areas infected with multiple orthopox viruses, especially in hotspots of mpox virus infections. [ABSTRACT FROM AUTHOR]

Smallpox was eradicated in less than 200 years after Edward Jenner's practice of cowpox variolation in 1796. The forty-three years of us living free of smallpox, beginning in 1979, never truly separated us from poxviruses. The recent outbreak of monkeypox in May 2022 might well warn us of the necessity of keeping up both the scientific research and public awareness of poxviruses. One of them in particular, the vaccinia virus (VACV), has been extensively studied as a vector given its broad host range, extraordinary thermal stability, and exceptional immunogenicity. Unceasing fundamental biological research on VACV provides us with a better understanding of its genetic elements, involvement in cellular signaling pathways, and modulation of host immune responses. This enables the rational design of safer and more efficacious next-generation vectors. To address the new technological advancement within the past decade in VACV research, this review covers the studies of viral immunomodulatory genes, modifications in commonly used vectors, novel mechanisms for rapid generation and purification of recombinant virus, and several other innovative approaches to studying its biology. [ABSTRACT FROM AUTHOR]

In African countries where mpox (monkeypox) is endemic, infection is caused by two genetically related clades—Clade I (formerly Congo Basin), and Clade IIa (formerly West Africa), both of which are potentially life-threatening infections. Prior to the 2022–2023 global outbreak, mpox infections among pregnant women caused by Clade I were reported to have a 75% perinatal case fatality rate in the Democratic Republic of Congo, including the only documented case of placental infection and stillbirth from the Congenital Mpox Syndrome, and the Clade IIa mpox infection was associated with stillbirths in Nigeria. The 2022–2023 global mpox outbreak, caused by a genetically distinct strain, Clade IIb, has focused attention on the effects of mpox on pregnant women and fetal outcomes. There have been at least 58 cases of mpox infection occurring in pregnant women during the 2022–2023 outbreak. No confirmed cases of adverse perinatal outcome, including stillbirth, have been reported. The absence of perinatal morbidity and mortality from Clade IIb corresponds to the overall case fatality rate among non-pregnant women of <0.1%, as this clade has been demonstrated to produce a less-severe disease than the mpox Clade I or IIa variants. Thus, there are apparently important differences between mpox clades affecting pregnant women and perinatal outcomes. [ABSTRACT FROM AUTHOR]

The purpose of this review is to give an up-to-date, thorough, and timely overview of monkeypox (Mpox), a severe infectious viral disease. Furthermore, this review provides an up-to-date treatment option for Mpox. The monkeypox virus (MPXV) has remained the most virulent poxvirus for humans since the elimination of smallpox approximately 41 years ago, with distribution mainly in central and west Africa. Mpox in humans is a zoonotically transferred disease that results in symptoms like those of smallpox. It had spread throughout west and central Africa when it was first diagnosed in the Republic of Congo in 1970. Mpox has become a major threat to global health security, necessitating a quick response by virologists, veterinarians, public health professionals, doctors, and researchers to create high-efficiency diagnostic tests, vaccinations, antivirals, and other infection control techniques. The emergence of epidemics outside of Africa emphasizes the disease's global significance. A better understanding of Mpox's dynamic epidemiology may be attained by increased surveillance and identification of cases. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Ornithology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We highlight a case of a 38‐year‐old immunocompromised man with untreated human immunodeficiency virus and Hepatitis C who presented with progressive soft tissue infection of the right foot despite appropriate antibiotic therapy. While he was admitted, the patient disclosed a recent diagnosis of mpox treated with oral tecovirimat. He subsequently developed worsening lesions over his entire body. In addition, a polymerase chain reaction of the wound on the right foot was positive for mpox virus, and the patient improved on treatment with intravenous tecovirimat and vaccinia immunoglobulin. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic demonstrated the need for potent and broad-spectrum vaccines. This study reports the development and testing of a lumpy skin disease virus (LSDV)-vectored vaccine against SARS-CoV-2, utilizing stabilized spike and conserved nucleocapsid proteins as antigens to develop robust immunogenicity. Construction of the vaccine (LSDV-SARS2-S,N) was confirmed by polymerase chain reaction (PCR) amplification and sequencing. In vitro characterization confirmed that cells infected with LSDV-SARS2-S,N expressed SARS-CoV-2 spike and nucleocapsid protein. In BALB/c mice, the vaccine elicited high magnitude IFN-γ ELISpot responses (spike: 2808 SFU/106 splenocytes) and neutralizing antibodies (ID50 = 6552). Testing in hamsters, which emulate human COVID-19 disease progression, showed the development of high titers of neutralizing antibodies against the Wuhan and Delta SARS-CoV-2 variants (Wuhan ID50 = 2905; Delta ID50 = 4648). Additionally, hamsters vaccinated with LSDV-SARS2-S,N displayed significantly less weight loss, lung damage, and reduced viral RNA copies following SARS-CoV-2 infection with the Delta variant as compared to controls, demonstrating protection against disease. These data demonstrate that LSDV-vectored vaccines display promise as an effective SARS-CoV-2 vaccine and as a potential vaccine platform for communicable diseases in humans and animals. Further efficacy testing and immune response analysis, particularly in non-human primates, are warranted. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has underscored the importance of swift responses and the necessity of dependable technologies for vaccine development. Our team previously developed a fast cloning system for the modified vaccinia virus Ankara (MVA) vaccine platform. In this study, we reported on the construction and preclinical testing of a recombinant MVA vaccine obtained using this system. We obtained recombinant MVA expressing the unmodified full-length SARS-CoV-2 spike (S) protein containing the D614G amino-acid substitution (MVA-Sdg) and a version expressing a modified S protein containing amino-acid substitutions designed to stabilize the protein a in a pre-fusion conformation (MVA-Spf). S protein expressed by MVA-Sdg was found to be expressed and was correctly processed and transported to the cell surface, where it efficiently produced cell–cell fusion. Version Spf, however, was not proteolytically processed, and despite being transported to the plasma membrane, it failed to induce cell–cell fusion. We assessed both vaccine candidates in prime-boost regimens in the susceptible transgenic K18-human angiotensin-converting enzyme 2 (K18-hACE2) in mice and in golden Syrian hamsters. Robust immunity and protection from disease was induced with either vaccine in both animal models. Remarkably, the MVA-Spf vaccine candidate produced higher levels of antibodies, a stronger T cell response, and a higher degree of protection from challenge. In addition, the level of SARS-CoV-2 in the brain of MVA-Spf inoculated mice was decreased to undetectable levels. Those results add to our current experience and range of vaccine vectors and technologies for developing a safe and effective COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

Background: The monkeypox outbreak in 2022 caused concern in the public. Infected patients usually present prodromal symptoms, such as lesions on their skin and mucous membranes, including the oral cavity. The current study aims to review the most common oral/perioral manifestations reported to date. Methods: A literature search was conducted in the PubMed, Research Gate, and Wiley Online Library databases, as well as in the Google search engine, using keywords related to the condition. Of the 56 publications identified, 30 were selected, including 27 case reports, two case series types, and one cross-sectional study published from 2003 to 2023 in endemic and non-endemic countries. Of the 54 patients in these studies, data on the oral symptoms and sites of monkeypox were interpreted from 47 patients. Results: Oral/perioral signs as one of the initial manifestations were reported in 23 out of 47 patients (48.93%). Out of the 47 patients with oral/perioral involvement, the most common signs/symptoms were sore throat, followed by ulcers, vesicles, dysphagia and odynophagia, and erythema. Conclusion: The most common oral symptom of monkeypox is sore throat, followed by ulcers. The symptoms usually occur in the pharynx/oropharynx, followed by the tonsils and tongue. Adequate knowledge about the characteristics of this virus and their association with the oral cavity is necessary, and could help oral health professionals to distinguish between different infections. [ABSTRACT FROM AUTHOR]