Baculoviruses are insect-specific pathogens. Novel baculovirus isolates provide new options for the biological control of pests. Therefore, research into the biological characteristics of newly isolated baculoviruses, including accurate classification and nomenclature, is important. In this study, a baculovirus was isolated from Mythimna separata and its complete genome sequence was determined by next-generation sequencing. The double-stranded DNA genome was 153 882 bp in length, encoding 163 open reading frames. The virus was identified as a variant of Mamestra brassicae multiple nucleopolyhedrovirus (MbMNPV) and designated Mamestra brassicae multiple nucleopolyhedrovirus CHN1 (MbMNPV-CHN1) according to ultrastructural analysis, genome comparison and phylogenetic analysis. Phylogenetic inference placed MbMNPV-CHN1 in a clade containing isolates of MacoNPV-A, MacoNPV-B and MbMNPV, which we have designated the Mb-McNPV group. The genomes of isolates in the Mb-McNPV group exhibited a high degree of collinearity with relatively minor differences in the content of annotated open reading frames. The development of codon usage bias in the Mb-McNPV group was affected mainly by natural selection. MbMNPV-CHN1 shows high infectivity against seven species of Lepidoptera. The yield of MbMNPV-CHN1 in the fourth- and fifth-instar M. separata larvae was 6.25×109-1.23×1010 OBs/cadaver. Our data provide insights into the classification, host range and virulence differences among baculoviruses of the Mb-McNPV group, as well as a promising potential new baculoviral insecticide.

Host control of mouse cytomegalovirus (MCMV) infection of MHCII- salivary gland acinar cells is mediated by CD4+ T cells, but how they protect is unclear. Here, we show CD4+ T cells control MCMV indirectly in the salivary gland, via IFNγ engagement with uninfected, but antigen+ MHCII+ APC and recruitment of NK cells to infected cell foci. This immune mechanism renders direct contact of CD4+ T cells with infected cells unnecessary and may represent a host strategy to overcome viral immune evasion.

The COVID-19 pandemic has highlighted the need for vaccines capable of providing rapid and robust protection. One way to improve vaccine efficacy is delivery via microarray patches, such as the Vaxxas high-density microarray patch (HD-MAP). We have previously demonstrated that delivery of a SARS-CoV-2 protein vaccine candidate, HexaPro, via the HD-MAP induces potent humoral immune responses. Here, we investigate the cellular responses induced by HexaPro HD-MAP vaccination. We found that delivery via the HD-MAP induces a type one biassed cellular response of much greater magnitude as compared to standard intramuscular immunization.

The most powerful approach to detect distant homologues of a protein is based on structure prediction and comparison. Yet this approach is still inapplicable to many viral proteins. Therefore, we applied a powerful sequence-based procedure to identify distant homologues of viral proteins. It relies on three principles: (1) traces of sequence similarity can persist beyond the significance cutoff of homology detection programmes; (2) candidate homologues can be identified among proteins with weak sequence similarity to the query by using 'contextual' information, e.g. taxonomy or type of host infected; (3) these candidate homologues can be validated using highly sensitive profile-profile comparison. As a test case, this approach was applied to a protein without known homologues, encoded by ORF4 of Lake Sinai viruses (which infect bees). We discovered that the ORF4 protein contains a domain that has homologues in proteins from >20 taxa of viruses infecting arthropods. We called this domain 'widespread, intriguing, versatile' (WIV), because it is found in proteins with a wide variety of functions and within varied domain contexts. For example, WIV is found in the NSs protein of tospoviruses, a global threat to food security, which infect plants as well as their arthropod vectors; in the RNA2 ORF1-encoded protein of chronic bee paralysis virus, a widespread virus of bees; and in various proteins of cypoviruses, which infect the silkworm Bombyx mori. Structural modelling with AlphaFold indicated that the WIV domain has a previously unknown fold, and bibliographical evidence suggests that it facilitates infection of arthropods.

Feline calicivirus (FCV) is considered one of the major pathogens of cats worldwide and causes upper respiratory tract disease in all cats. In some cats, infection is by a highly virulent strain of FCV (vs.-FCV), which can cause severe and fatal systemic disease symptoms. At present, few antiviral drugs are approved for clinical treatment against FCV. Therefore, there is an imminent need for effective FCV antiviral agents. Here, we used observed a cytopathic effect (CPE) assay to screen 1746 traditional Chinese medicine monomer compounds and found one that can effectively inhibit FCV replication, namely, handelin, with an effective concentration (EC50) value of approximately 2.5 µM. Further study showed that handelin inhibits FCV replication via interference with heat shock protein 70 (HSP70), which is a crucial host factor and plays a positive role in regulating viral replication. Moreover, handelin and HSP70 inhibitors have broad-spectrum antiviral activity. These findings indicate that handelin is a potential candidate for the treatment of FCV infection and that HSP70 may be an important drug target.

Parainfluenza virus type 5 (PIV5) can either have a persistent or a lytic phenotype in cultured cells. We have previously shown that the phenotype is determined by the phosphorylation status of the phosphoprotein (P). Single amino acid substitutions at critical residues, including a serine-to-phenylalanine substitution at position 157 on P, result in a switch between persistent and lytic phenotypes. Here, using PIV5 vectors expressing either mCherry or GFP with persistent or lytic phenotypes, we show that in co-infections the persistent phenotype is dominant. Thus, in contrast to the cell death observed with cells infected solely with the lytic variant, in co-infected cells persistence is immediately established and both lytic and persistent genotypes persist. Furthermore, 10-20 % of virus released from dually infected cells contains both genotypes, indicating that PIV5 particles can package more than one genome. Co-infected cells continue to maintain both genotypes/phenotypes during cell passage, as do individual colonies of cells derived from a culture of persistently infected cells. A refinement of our model on how the dynamics of virus selection may occur in vivo is presented.

Qinviridae is a family of negative-sense RNA viruses with genomes of 7.3-8.2 kb that have been associated with crustaceans, insects, gastropods, and nematodes. The qinvirid genome consists of two segments, each with at least one open reading frame (ORF). The large (L) segment ORF encodes a large protein containing an RNA-directed RNA polymerase (RdRP) domain. The small (S) segment ORF encodes a nucleocapsid protein. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Qinviridae, which is available at ictv.global/report/qinviridae.

The recent discovery of Bourbon virus (BRBV) put a new focus on the genus of thogotoviruses as zoonotic, tick-transmitted pathogens within the orthomyxovirus family. Since 2014, BRBV has been linked to several human cases in the Midwest United States with severe acute febrile illness and a history of tick bites. The detection of the virus in the Lone Star tick, Amblyomma americanum, and a high sero-prevalence in wild animals suggest widespread circulation of BRBV. Phylogenetic analysis of the viral RNA genome classified BRBV into the subgroup of Dhori-like thogotoviruses. Strikingly, BRBV is apathogenic in mice, contrasting not only with the fatal disease in affected patients but also with the severe disease in mice caused by other members of the thogotovirus genus. To gain insights into this intriguing discrepancy, we will review the molecular biology and pathology of BRBV and its unique position within the thogotovirus genus. Lastly, we will discuss the zoonotic threat posed by this newly discovered pathogen.

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating pathogens to the global swine industry. Many commercial PRRSV vaccines, originally designed to provide homologous protection, have shown partial protection against heterologous strains. However, the protective immune mechanisms mediated by these PRRSV vaccines are not fully understood. In this study, we investigated the factors responsible for partial protection conferred by an attenuated Chinese HP-PRRSV vaccine (TJM-F92) against heterologous NADC30-like PRRSV. By analysing peripheral T-cell responses induced by the TJM-F92 vaccine and local and systemic memory responses following challenge with NADC30-like PRRSV (SD17-38 strains) as well as neutralizing antibody response, we found that the TJM-F92 vaccine induced a significant expansion of CD8 T cells but not CD4 T cells or γδ T cells. The expanded CD8 T cells exhibited a phenotype of effector memory T cells and secreted IFN-γ upon restimulation with SD17-38 strains in vitro. In addition, only CD8 T cells in the prior immunized pigs rapidly expanded in the blood and spleen after heterologous challenge, with higher magnitude, compared to the unvaccinated pigs, showing a remarkable memory response. In contrast, no obvious humoral immune response was enhanced in the vaccinated and challenged pigs, and no heterologous neutralizing antibodies were detected throughout the experiment. Our results suggested that CD8 T cells elicited by the TJM-F92 vaccine may be responsible for partial heterologous protection against NADC30-like PRRSV strains and potentially recognize the conserved antigens among PRRSV strains.

The neuraminidase inhibitor (NAI) oseltamivir is stockpiled globally as part of influenza pandemic preparedness. However, oseltamivir carboxylate (OC) resistance develops in avian influenza virus (AIV) infecting mallards exposed to environmental-like OC concentrations, suggesting that environmental resistance is a real concern. Herein we used an in vivo model to investigate if avian influenza H1N1 with the OC-resistant mutation NA-H274Y (51833/H274Y) as compared to the wild-type (wt) strain (51833 /wt) could transmit from mallards, which would potentially be exposed to environmentally contaminated environments, to and between chickens, thus posing a potential zoonotic risk of antiviral-resistant AIV. Regardless of whether the virus had the OC-resistant mutation or not, chickens became infected both through experimental infection, and following exposure to infected mallards. We found similar infection patterns between 51833/wt and 51833/H274Y such that, one chicken inoculated with 51833/wt and three chickens inoculated with 51833/H274Y were AIV positive in oropharyngeal samples more than 2 days consecutively, indicating true infection, and one contact chicken exposed to infected mallards was AIV positive in faecal samples for 3 consecutive days (51833/wt) and another contact chicken for 4 consecutive days (51833/H274Y). Importantly, all positive samples from chickens infected with 51833/H274Y retained the NA-H274Y mutation. However, none of the virus strains established sustained transmission in chickens, likely due to insufficient adaptation to the chicken host. Our results demonstrate that an OC-resistant avian influenza virus can transmit from mallards and replicate in chickens. NA-H274Y does not constitute a barrier to interspecies transmission per se, as the resistant virus did not show reduced replicative capacity compared to the wild-type counterpart. Thus, responsible use of oseltamivir and surveillance for resistance development is warranted to limit the risk of an OC-resistant pandemic strain.