Journal of Virology最新文献

{"title":"PEX19 restricts porcine deltacoronavirus replication through farnesylation-dependent and -independent mechanisms.","authors":"Chaoqun Chen, Guanning Su, Yuchen Wang, Yuanxiang Xiong, Wenwen Xiao, Zhuang Li, Liurong Fang, Yanrong Zhou, Shaobo Xiao","doi":"10.1128/jvi.02097-25","DOIUrl":"10.1128/jvi.02097-25","url":null,"abstract":"<p><p>Peroxisomes are vital cellular organelles that play critical roles in metabolism, immune regulation, and disease pathogenesis. As a key receptor for peroxisomal membrane proteins, peroxisomal biogenesis factor 19 (PEX19) is essential for peroxisome biogenesis. In this study, we identify PEX19 as a novel host restriction factor against porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus with zoonotic potential. Overexpression of PEX19 significantly inhibits PDCoV replication, while knockout of PEX19 enhances viral propagation. Interestingly, the anti-PDCoV effect of PEX19 largely depends on its farnesylation modification, as PEX19 mutants with deleted or mutated farnesylation sites exhibit only marginal anti-PDCoV activity. Mechanistically, PEX19 restricts PDCoV infection through three distinct pathways: (i) reducing cellular cholesterol levels in a farnesylation-dependent manner, (ii) targeting the viral nonstructural protein 2 (nsp2) for autophagy-lysosome-mediated degradation, which is also dependent on farnesylation, and (iii) inducing low-level interferon production independently of farnesylation. Taken together, these findings define a new antiviral role for PEX19 and highlight its potential as a therapeutic target for combating PDCoV infection.IMPORTANCEPeroxisomes are increasingly recognized as critical regulators of virus-host interactions; however, their roles during coronavirus infection remain poorly understood and controversial. By screening the peroxins (PEXs) that regulate the replication of porcine deltacoronavirus (PDCoV), we identify PEX19, a key peroxisomal biogenesis factor, as a novel antiviral host protein, whose anti-PDCoV activity is largely dependent on farnesylation modification. Our findings demonstrate that farnesylated PEX19 restricts PDCoV replication by reducing cellular cholesterol levels and promoting autophagy-lysosome-mediated degradation of the viral nsp2 protein, while also inducing low-level interferon production independently of farnesylation. These results provide new molecular insights into PDCoV-host interactions and highlight PEX19 as a potential therapeutic target against PDCoV infection.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0209725"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PEDV regulates trans-mammary epithelial migration of T cells in a CCR10/CCL28-dependent manner.","authors":"Yuwei Zhai, Yajuan Ma, Chaofan Liu, Yanan Zhang, Feiyan Wang, Qingbo Shi, Qinye Song, Chen Yuan","doi":"10.1128/jvi.00024-26","DOIUrl":"10.1128/jvi.00024-26","url":null,"abstract":"<p><p>Porcine epidemic diarrhea virus (PEDV) is a re-emerging coronavirus that infects neonatal piglets via newly discovered colostrum transmission routes. Research has shown that T cells carrying PEDV in colostrum can infect piglets, but the mechanism is unclear. This study revealed that PEDV impairs T-cell immune function, preventing the production of granzymes, perforin, and interferon-γ. Furthermore, RNA sequencing of PEDV-infected and uninfected T cells revealed significant differences in gene expression: the expression of CCR10 on T-cell surfaces increased, whereas the expression of vinculin, α-actinin, paxillin, FAK, and talin-1 decreased (<i>P</i> < 0.05). The results revealed that CCR10 only interacts with CCL28. PEDV strains led to significant upregulation of CCL28 in porcine mammary epithelial cells (PMECs). Finally, the role of CCR10/CCL28 in T-cell migration during PEDV infection was illustrated via a small interfering RNA (siRNA)-mediated knockdown method and a coculture model of PMECs with T cells. The results demonstrated that the addition of the chemokine CCL28 to the lower chamber of the transwell system elicits a chemotactic effect on T cells. This phenomenon is attributed mainly to the substantial increase in the expression levels of paxillin and FAK on the surface of T cells following siRNA-mediated interference with CCR10. In contrast, no significant differences were observed in the expression levels of vinculin and α-actinin. These results suggest a mechanism underlying the regulation of T-cell migration in response to CCL28, which is potentially associated with the modulation of paxillin and FAK expression levels.</p><p><strong>Importance: </strong>Understanding the impact of porcine epidemic diarrhea virus (PEDV) on T-cell function and migration is crucial. This study reveals PEDV impairs T-cell immunity by preventing key molecule production. It uncovers significant gene expression changes in infected T cells, with CCR10 rising and several adhesion-related proteins falling. Further, CCR10 interacts solely with CCL28, and PEDV upregulates CCL28 in PMECs, is key. The transwell system experiments show CCL28's chemotactic effect on T cells, linked to paxillin and FAK expression changes. These findings shed light on how PEDV manipulates T-cell migration via the CCR10/CCL28 axis, aiding in developing strategies against PEDV.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0002426"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining the transmissible dose 50% for two pandemic influenza viruses in ferrets.","authors":"C J Field, K M Septer, D R Patel, V C Weaver, D G Sim, K H Restori, M F Boni, T C Sutton","doi":"10.1128/jvi.01635-25","DOIUrl":"10.1128/jvi.01635-25","url":null,"abstract":"<p><p>Ferrets are widely used to model airborne transmission of influenza viruses in humans. Airborne transmission is evaluated by infecting donor ferrets with a high virus dose and monitoring transmission to contact animals sharing the same airspace. Humans can be infected with a broad range of influenza virus doses. Therefore, we evaluated the relationship between inoculation dose and transmission for two pandemic influenza viruses in ferrets. Donor ferrets were inoculated with 10⁰ to 10⁶ tissue culture infectious dose 50 (TCID₅₀) of the 2009 pandemic H1N1 or 1968 pandemic H3N2 virus and were then paired with respiratory contacts. Using the proportion of donors that became infected across virus doses, we calculated the infectious dose 50 (ID₅₀). Subsequently, by comparing the proportion of contacts that became infected, we calculated the transmissible dose 50% (TD₅₀): the donor inoculation dose that resulted in transmission to 50% of contacts. For the 2009 pandemic H1N1 virus, the ID₅₀ and TD₅₀ were equivalent at <1 TCID₅₀. However, for the 1968 pandemic H3N2 virus, the ID₅₀ and TD₅₀ were 10^0.5 and 10^4.08 TCID₅₀ (95% CI: 10^2.34-10^5.82), respectively. The increased TD₅₀ for the H3N2 virus was associated with significant reductions in peak viral titers and viral shedding in donors over decreasing virus inoculation doses. Collectively, these studies define a new measure of transmission that permits comparisons of transmissibility between viral strains and subtypes in ferrets. We show that the 1968 pandemic H3N2 virus has a higher TD₅₀ and reduced transmissibility in ferrets relative to the 2009 pandemic H1N1 virus.</p><p><strong>Importance: </strong>Ferrets are the gold standard animal model used to assess the transmissibility of influenza viruses. Airborne transmission is evaluated by infecting donor ferrets with a high virus dose and monitoring transmission to contact animals sharing the same airspace. However, the relationship between inoculation dose and transmission has not been evaluated in ferrets. Therefore, we performed studies evaluating airborne transmission of the 2009 pandemic H1N1 and 1968 pandemic H3N2 viruses over log scale reductions in donor inoculation doses. Using the results of these studies, we define a new measure of transmission, the transmissible dose 50%: the donor inoculation dose at which a virus is transmitted to 50% of contacts. Importantly, this metric permits the evaluation of transmissibility over a log scale. We demonstrate that the 1968 pandemic H3N2 virus has reduced transmissibility compared to the 2009 pandemic H1N1 virus in ferrets.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0163525"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and phylogenetic analyses of umbravirus and umbra-like virus genomes suggest evolution of capsid-like proteins from 30K movement proteins.","authors":"Anne E Simon, Jason M Needham, Anna Mikkelsen, Osama Atallah","doi":"10.1128/jvi.02209-25","DOIUrl":"10.1128/jvi.02209-25","url":null,"abstract":"<p><p>Plant umbraviruses (UVs) encode, in embedded open reading frames, an unstructured movement protein (MP) (ORF3) required for vascular long-distance movement and a structured 30K-type MP (ORF4) for cell-to-cell movement. UVs do not encode capsid proteins and require helper viruses for vector acquisition. Umbra-like viruses (ULVs) comprise two groups whose RNA-dependent RNA polymerases share significant similarity with UVs and whose non-replicase ORFs, if any, are either single, embedded, or separate. Group 2 ULVs, which lack encoded MPs, use a host-encoded MP and do not require a helper virus, presumably due to encoding a capsid-like protein. Group 1 ULVs are more closely related to UVs and have been identified in Ageratum, Arborvitae, <i>Paspalum paspaloides</i>, switchgrass, and grapevine. Structural and phylogenetic analyses of Group 1 ULVs suggest that ULVs evolved from UVs following the loss of ORF3, duplication of 30K MP ORF 4, recombination to remove an intergenic region, and evolution of the paralog ORF4s to encode a capsid-like protein and a protein of unknown function. Neither duplicated ORF in Group 1 grapevine GULV4 was required for systemic infection of <i>Nicotiana benthamiana</i>. Structural comparisons of 17 UV and 8 Group 1 ULV frameshifting sites revealed strong conservation, including two previously unknown hairpins and pseudoknots that were absent in Group 2 ULVs. Group 1 ULVs also contain I-shaped structure (ISS) 3' cap-independent translation enhancers with novel conformations not found in UVs or Group 2 ULVs. These and other findings comprise a baseline of knowledge that will inform further experimental examination of these unique viruses.IMPORTANCEThe key defining feature of plant viruses is their encoding of movement proteins (MPs), with most from a superfamily of MPs known as 30K. It has been proposed that 30K MPs evolved from capsid proteins, as both contain similar \"jelly roll\" domains. Umbraviruses encode two MPs in overlapping ORFs, with ORF4 encoding a 30K-type MP. Umbraviruses and umbra-like viruses (ULVs) have related replication proteins (ORFs 1 and 2) but differ in their non-replication ORFs. Recently, Group 2 ULVs were found to encode a capsid-like protein and no MPs, relying instead on host proteins for movement. Current investigation of the sequences and structures of Group 1 ULVs, which contain one or two ORFs of unknown function, revealed that ULVs likely evolved from umbraviruses following duplication of the 30K MP ORF and neofunctionalizations to a jelly roll-containing capsid-like protein and a second non-MP, suggesting that capsid proteins can also evolve from MPs.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0220925"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Src family kinases Fyn and Lyn in arenavirus infection.","authors":"Wenting Mao, Minmin Zhou, Cheng Peng, Yi Wan, Li Li, Jialing Hu, Yang Liu, Yuan Peng, Chao Shan, Fei Deng, Zhiming Yuan, Wei Wang","doi":"10.1128/jvi.00241-26","DOIUrl":"10.1128/jvi.00241-26","url":null,"abstract":"<p><p>Arenaviruses encompass a diverse group of infectious agents, some of which, like Lassa virus (LASV), pose significant threats to global public health due to their acute virulence, while others, such as lymphocytic choriomeningitis virus (LCMV), are less pathogenic but still clinically relevant. Both Old World arenaviruses LASV and LCMV exploit host tyrosine kinase signaling to establish infection, though the molecular mechanisms remain incompletely understood. In this study, phosphorylated receptor tyrosine kinase antibody array screening revealed that recombinant LASV (rLCMV-LASV GP) infection specifically activates Src family kinases (SFKs), Fyn and Lyn, with their phosphorylation levels markedly elevated during early infection. Subsequent co-immunoprecipitation assays confirmed rLCMV-LASV GP-induced tyrosine phosphorylation of Fyn and Lyn activation. RNAi experiments demonstrated that knockdown of Fyn/Lyn significantly suppressed rLCMV-LASV GP and LCMV nucleocapsid protein expression, viral RNA synthesis, and viral production, highlighting the critical role of SFKs in viral infection. Further investigations showed that saracatinib, an Src inhibitor, exhibited broad-spectrum antiviral activity against LCMV strains, as well as the authentic LASV strain Lassa_HX strain. <i>In vivo</i> studies revealed that saracatinib substantially reduced viral loads in splenic and hepatic tissues and alleviated infection-associated histopathological damage. These findings identify Src family kinase Fyn/Lyn as novel host targets for arenavirus and provide new targets of prevention and treatment for arenaviral infection.IMPORTANCEArenaviruses, including the highly pathogenic Lassa virus (LASV) and clinically relevant lymphocytic choriomeningitis virus (LCMV), pose severe global health threats due to limited therapeutic options. This study unveils a critical host-pathogen interaction mechanism by which Src family kinases (SFKs) Fyn and Lyn facilitate LASV and LCMV infection. Through phosphorylation profiling and functional validation, we establish that viral activation of these kinases drives arenavirus infection. Moreover, the FDA-approved Src inhibitor saracatinib exhibits broad-spectrum efficacy, suppressing LCMV strains as well as the authentic LASV <i>in vitro</i>, while reducing LCMV viral loads and histopathology <i>in vivo</i>. These findings redefine tyrosine kinases as host targets, offering a novel host-directed antiviral strategy by repurposing existing clinical compounds.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0024126"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-neutralization and antigenic characterization of simian and equine group A rotaviruses.","authors":"Shalini Soni, Lianne G Eertink, Ni Shuisong, Alan Loynachan, Samantha M Barnum, Emma N Adam, Michael A Kennedy, Dan Wang, Feng Li","doi":"10.1128/jvi.00199-26","DOIUrl":"10.1128/jvi.00199-26","url":null,"abstract":"<p><p>Rotaviral diarrhea in foals is caused by two dominant G3P[12] and G14P[12] genotypes of equine rotavirus A (ERVA). Protection of foals against ERVA infection and disease is achievable by passive antibody transfer through colostrum from mares receiving inactivated monovalent G3P[12] vaccine. Simian rotavirus SA11 G3P[2] is also included in ERVA vaccines to protect foals. Here, we characterized cross-neutralization and protection among three distinctive rotaviruses carrying the same or different G (defined by VP7) or P (defined by VP4) genotype by using a rabbit and equine monospecific antisera panel coupled with structural and computational analyses of viral epitopes. Data from these experiments demonstrated that (i) rSA11 G3P[2] and equine G3P[12] neutralized well with each other in rabbit antisera but with less cross-neutralization capacity against equine G14P[12]; (ii) interestingly, rabbit antisera to equine G14P[12] provided more robust cross-protection against rSA11 G3P[2] than the reverse; (iii) despite only a few amino acid differences in VP8* between two equine viruses, rabbit antisera to VP8* of equine G3P[12] moderately cross-neutralized G14P[12] but with potent neutralizing activity against rSA11 G3P[2]; (iv) surprisingly, the breadth and magnitude of cross-neutralization among three viruses in equine antisera were broader and stronger than those observed in rabbit antisera; and (v) multiple highly solvent-exposed amino acid residues conserved in VP7 and VP8* among three viruses may serve as novel B cell epitopes that contribute to the observed cross-neutralization. Taken together, these results highlight that cross-neutralization determinants among different rotaviruses are complex and dependent on specific viral context and animal species.</p><p><strong>Importance: </strong>Our findings support that the G genotype determined by the VP7 protein plays a more important role, within the virus panel examined in this study, in determining broad neutralization specificity than previously thought. Our work has implications for vaccine design, suggesting that the inclusion of diverse G genotypes may be necessary to achieve broader protection. The P genotype, determined by the VP4 protein, exhibited variable levels of cross-neutralization, indicating that the P genotype alone may not be sufficient to induce strong cross-neutralization among different rotaviral strains. G genotype- or VP7-driven cross-protection may be conferred by novel epitopes identified structurally in this study. Finally, our study revealed that horse sera were more capable of cross-neutralizing different equine and simian rotaviruses than rabbit sera. This finding has implications for vaccine development, underscoring the need to evaluate candidate vaccines across multiple species or in species-relevant models to ensure broad and effective vaccine-mediated protection against rotavirus infection.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0019926"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of thermostability-enhancing mutations in H9N2 avian influenza virus hemagglutinin.","authors":"Binjian Liu, Hai Yu, Zhanfei Yan, Shuping Zou, Jinyue Guo, Shan Cai, Yingqin Hu, Yu Yang, Yulin Yan, Hao Liu, Kun Mei, Zhili Li, Limei Qin, Yong Li, Shujian Huang, Feng Wen","doi":"10.1128/jvi.00168-26","DOIUrl":"10.1128/jvi.00168-26","url":null,"abstract":"<p><p>H9N2 avian influenza viruses (AIVs) remain a significant economic burden on poultry production and a persistent zoonotic threat. Hemagglutinin (HA), a surface glycoprotein mediating viral entry and pathogenesis, critically depends on thermostability for its function. Our previous study indicated that recent H9N2 AIVs have experienced a reduction in hemagglutination activity and exhibit low HA thermostability; however, the underlying molecular determinants for this instability remain poorly defined. To address this gap, we employed an <i>in vitro</i>-directed evolution approach to identify HA mutations that enhance thermostability. By subjecting a diverse HA mutant library to iterative heat selection at 48°C, we isolated several HA-stabilizing mutations, including L29I, N133S, N210D, G266R, D387N, A423T, and E509G, and confirmed their effect by site-directed mutagenesis. Further characterization revealed a complex interplay between HA stability, receptor binding specificity, and acid tolerance. Our findings demonstrate that enhancing HA stability can exert pleiotropic effects on key viral properties, highlighting the importance of understanding these relationships for developing effective mitigation strategies against H9N2 AIVs.</p><p><strong>Importance: </strong>H9N2 avian influenza viruses pose a persistent threat to poultry production and human health, demanding improved control strategies. This study addresses a key knowledge gap by uncovering the molecular determinants that modulate the stability of the hemagglutinin (HA) protein in H9N2 viruses. We identify specific HA mutations that increase thermostability, a property potentially linked to environmental persistence. Furthermore, our findings demonstrate a critical interplay between HA stability and essential viral functions, including receptor binding, hemagglutination activity, replication kinetics, and overall acid tolerance. By disentangling these properties, we provide insights into the mechanisms underlying HA-mediated viral entry and infectivity, which could inform the development of more effective vaccines and therapeutics.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0016826"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147468774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type I interferon signaling is required for resistance to primary influenza virus infection and vaccine-induced long-term immunity.","authors":"Ki-Hye Kim, Hye Suk Hwang, Surya Sekhar Pal, Chau Thuy Tien Le, Phillip Grovenstein, Mahmuda Yeasmin, Jae Min Song, Young-Man Kwon, Baozhong Wang, Sang-Moo Kang","doi":"10.1128/jvi.00229-26","DOIUrl":"10.1128/jvi.00229-26","url":null,"abstract":"<p><p>Type I interferons (IFNs) are critical for early antiviral defense, yet their role in shaping vaccine-induced immunity remains incompletely understood. Here, we investigated the impact of type I IFN receptor (IFNαβR) deficiency on immune responses to influenza virus infection and vaccination in IFNαβR-deficient (AB6) mice. AB6 mice exhibited profound susceptibility to influenza virus infection, characterized by accelerated weight loss, elevated lung viral loads, and severe histopathology. Despite inducing short-term IgG antibodies and protection against weight loss after H5 hemagglutinin virus-like particle (H5 VLP) vaccination, AB6 mice were less effective in controlling lung viral loads and inflammation after lethal influenza virus infection, compared to the wild-type (B6) mice. IFNαβR deficiency dysregulated chemokines and numerous innate immune cells, particularly neutrophils, contributing to lung pathology after H5 VLP vaccination and influenza virus infection. AB6 mice exhibited a faster kinetics of waning IgG antibodies and lower efficacy of long-term protection after vaccination than wild-type B6 mice.IMPORTANCEType I interferons (IFNs) are essential mediators of antiviral defense, but their contribution to vaccine-induced immunity remains unclear. This study reveals that type I IFN receptor signaling is dispensable for the initial antibody induction but is critical for sustaining long-term humoral immunity and balanced immune regulation after influenza vaccination and infection. Loss of IFNαβR signaling leads to impaired viral control, excessive neutrophil-driven inflammation, and disrupted immune cell homeostasis. These findings highlight type I IFN signaling as a key integrator of innate and adaptive immune responses required for adequate and durable antiviral protection.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0022926"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147530313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the enigmatic biology of arteriviruses through receptor discovery.","authors":"Adam L Bailey","doi":"10.1128/jvi.01787-25","DOIUrl":"10.1128/jvi.01787-25","url":null,"abstract":"<p><p>Arteriviruses are diverse +ssRNA viruses (<i>Nidovirales</i> Order; <i>Arteriviridae</i> Family) that infect a variety of mammals. Arterivirus infections can manifest in a variety of ways, ranging from viral hemorrhagic fever to persistent sub-clinical infection. A perplexing feature of arterivirus biology is the unusual network of small glycoproteins that decorate the virion surface. How these glycoproteins mediate viral entry into target cells remains poorly understood, but it is widely accepted that the arterivirus entry process is novel. This review highlights recent advances in the characterization of arterivirus entry receptors and examines unique features of arterivirus biology-including disease, persistence, tropism, evolution, and cross-species transmission-through the lens of receptor utilization.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0178725"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV transgenic mouse monocytes display increased <i>in vivo</i> migration across the blood-brain barrier associated with increased expression of genes associated with mononuclear leukocyte movement.","authors":"Agnes Sydenstricker, Danica Lee, Adilyn Voss, Jian Hua Zheng, Hong Hur, Manoj Kandpal, Harris Goldstein","doi":"10.1128/jvi.02063-25","DOIUrl":"10.1128/jvi.02063-25","url":null,"abstract":"<p><p>Soon after HIV acquisition, circulating HIV-infected monocytes cross the blood-brain barrier (BBB) and infect resident brain microglia and other susceptible cells, establishing a potential viral reservoir. Despite suppressive antiretroviral therapy, these HIV-infected cells mediate a neuroinflammatory process causing HIV-associated neurocognitive deficits (HAND) in at least 20% of people with HIV. Continued migration of HIV-infected monocytes into the brain may further exacerbate neuroinflammation and replenish viral reservoirs. To ascertain how HIV infection facilitates monocyte passage across the BBB <i>in vivo</i>, we developed a novel mouse model to quantify circulating monocytes supporting HIV production that migrated into the brain. We demonstrate that significantly more monocytes from HIV-transgenic mice, capable of supporting HIV production, crossed the BBB compared to control transgenic mouse monocytes. This difference was particularly pronounced after recipient mice were treated with lipopolysaccharide (LPS). To explore the underlying mechanism, we compared the transcriptomes of HIV transgenic mouse monocytes and control mouse monocytes and identified multiple differentially expressed genes linked to mononuclear leukocyte trafficking, including several associated with monocyte chemotaxis. We also evaluated the effect of substance use in combination with HIV infection on monocyte migration across the BBB into the brain by treating HIV transgenic mice with either morphine or methamphetamine. Short-term exposure to either drug did not significantly alter the migration of HIV-transgenic monocytes across the BBB.IMPORTANCEOver 20% of people with HIV (PWH) develop cognitive and neurological deficits despite antiretroviral therapy. While the blood-brain barrier (BBB) normally prevents brain entry of circulating monocytes, HIV enables infected monocytes to traverse the BBB, establish viral production within the brain, and subsequently infect microglia and other cells, which drives neuroinflammation, neuronal injury, and neurocognitive impairment. To investigate how HIV stimulates <i>in vivo</i> migration of circulating monocytes across the BBB, we developed a novel mouse model utilizing HIV-transgenic mouse monocytes that support HIV production. After intravenous injection, a significantly higher number of HIV-transgenic monocytes migrated into the brains of wild-type mice compared to control transgenic monocytes, particularly after lipopolysaccharide (LPS) treatment. We identified multiple genes differentially expressed in HIV-transgenic monocytes associated with mononuclear leukocyte trafficking linked to HIV-mediated induction of monocyte transmigration across the BBB. These genes may represent therapeutic targets to prevent HIV-infected monocyte migration into the brain.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0206325"},"PeriodicalIF":3.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}