Journal of Virology最新文献

{"title":"Metformin hydrochloride regulates glycolysis and inhibits PEDV replication by inhibition of PI3K-AKT signaling pathway.","authors":"Xingcui Zhang, Yi Li, Jianbo Yuan, Qingyang Li, Xiaoru Hu, Ziyan Song, Zhiwei Sun, Yanwen Song, Yi Zhong, Guisong Liao, Jinman Ding, Shu Yang, Zhenhui Song","doi":"10.1128/jvi.00147-26","DOIUrl":"10.1128/jvi.00147-26","url":null,"abstract":"<p><p>Viruses rely on energy and biosynthetic materials of host cell from glucose metabolism to support their replication, and glucose plays a crucial role in viral infection. In this study, we found that porcine epidemic diarrhea virus (PEDV) infection significantly increased cellular glucose uptake and stimulated the production of the glycometabolite lactate. Exogenous supplementation of glucose or L-lactate confirmed that it significantly promoted PEDV proliferation, indicating that replication of PEDV was enhanced by regulating host glucose metabolism, particularly reprogramming glycolysis. Based on these findings, we explored the potential antiviral approach targeting the virus through regulating glycolytic processes. Metformin hydrochloride (MH) is a well-known hypoglycemic agent, which has shown notable anti-PEDV activity. After MH treatment, the transcriptome analysis showed the differential genes were mainly enriched in PI3K-AKT signaling pathway, and the expression levels of its downstream molecule GSK3B and MYC were significantly upregulated and downregulated, respectively. The gene expression related to glycolysis was also significantly inhibited. Further experiments showed that MH significantly inhibited the phosphorylation of AKT and its translocation to plasma membrane, while reducing the phosphorylation level of GSK3B. MH maintained GSK3B in a non-phosphorylated state by blocking the activation of the EGFR/PI3K/AKT/GSK3B pathway, mediated the degradation of c-MYC through phosphorylation, inhibited the glycolysis process, reduced the production of lactic acid, and finally exerted its antiviral effect. This study demonstrated that PEDV infection could induce glycolysis through metabolic reprogramming, thereby promoting viral replication; whereas, MH was able to effectively reverse this process, significantly inhibiting the virus-induced glycolysis pathway and exhibiting antiviral activity.IMPORTANCEThis study aims to elucidate the antiviral effects and molecular mechanisms of MH against PEDV. The results show that MH can inhibit the activation of the PI3K-AKT signaling pathway induced by PEDV infection, thereby suppressing the production of the glycolytic product L-lactic acid and ultimately resisting PEDV infection. This research provides new insights into the prevention and control of PEDV and offers scientific evidence for the application of MH in veterinary medicine.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0014726"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504325","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":"Pantanal virophage: a new virophage species associated with a moumouvirus and a transpoviron, expanding the genus <i>Sputnikvirus</i>.","authors":"Bruna Luiza de Azevedo, Nidia Esther Colquehuanca Arias, Talita Bastos Machado, João Pessoa Araújo Júnior, Ana Karoline da Nóbrega Nunes Alves, Luiz Carlos Junior Alcantara, Frank O Aylward, Luiz Henrique Rosa, Rodrigo Araújo Lima Rodrigues, Jônatas Santos Abrahão","doi":"10.1128/jvi.01930-25","DOIUrl":"10.1128/jvi.01930-25","url":null,"abstract":"<p><p>Amoeba-infecting giant viruses, such as mimiviruses, challenged paradigms of virology since their discovery. Their extensive and complex genomes and particle structures can interact with virophages and transpovirons, revealing unique aspects of the viral ecology and evolution. Here, we describe the isolation of Pantanal virophage, a new virophage obtained from Brazilian pantanal biome. The virophage was found in association with moumouvirus pantanense and a transpoviron sequence. Sequencing and genomic analysis revealed that Pantanal virophage presents a 17,964 bp genome with 21 coding sequences, including two ORFans that code for proteins with completely unknown functions. Phylogeny showed that Pantanal virophage composes a divergent branch within virophages from <i>Sputnikvirus</i> genus. Average nucleotide and amino acid identity analysis comparing different virophage sequences indicated that Pantanal virophage could represent a new <i>Sputnikvirus</i> species. These findings shed light on the giant virus-virophage-transpoviron triplet diversity, evolution, and ecology, contributing to a future update in virophages taxonomy.IMPORTANCEStudies on prospecting, isolation, and characterization of new amoeba viruses are important to provide new information about biology, diversity, evolution, ecology, and taxonomy of these viruses. This work reinforces this importance since we describe Pantanal virophage, a new species of Sputnikvirus found in association with a moumouvirus and a transpoviron. The characterization of Pantanal virophage provided new data and observations regarding the phylogeny and taxonomy of <i>Sputnikvirus</i> genus evidencing the need for constant updates in taxonomic classification. This work shows that the efforts for isolation of new amoeba viruses and their characterization can contribute to enriching the knowledge about taxonomy and evolutionary dynamics of these viruses and of their parasitic-associated elements.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0193025"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592933","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":"Disruption of spike protein N-glycosylation induces its endoplasmic reticulum retention and attenuates SARS-CoV-2 infectivity.","authors":"Weili Kong, Jiali Zhang, Yingying Song, Jingjing Song, Yuebo Xu, Xinmu Xu, Haoyu Ma, Li Chen, Cong Zeng","doi":"10.1128/jvi.00270-26","DOIUrl":"10.1128/jvi.00270-26","url":null,"abstract":"<p><p>The spike (S) protein of SARS-CoV-2 is extensively glycosylated, with N-glycosylation sites remaining highly conserved during viral evolution. While inhibiting N-glycosylation has been shown to significantly suppress SARS-CoV-2 infection, the underlying molecular mechanisms remain incompletely characterized. Here, we identify that two N-glycosylation sites, N61 and N343, are critical for spike maturation. We demonstrate that asparagine-to-aspartic acid substitutions (N to D) at these sites lead to endoplasmic reticulum (ER) retention of the S protein, with consequent abrogation of S1/S2 cleavage and near-complete elimination of viral infectivity. IP-MS analysis further reveals that the COPI complex, which facilitates retrograde Golgi-to-ER transport, is a key participant in this ER retention process. Additionally, inhibition of COPI effectively restores the plasma membrane localization of N61D- and N343D-mutated S proteins and enhanced viral infectivity. More importantly, a specific inhibitor has been developed that effectively blocks the ER-to-Golgi trafficking of the S protein, thereby broadly abolishing viral infectivity across SARS-CoV-2 variants. Overall, our study reveals the unique roles of N-glycosylation in the regulation of S protein maturation, providing a potential mechanistic target for antiviral drug development.IMPORTANCEN-glycosylation of the spike protein is critical for SARS-CoV-2. While most studies have focused on the effects on spike-ACE2 binding and neutralizing antibody recognition, few studies have reported how N-glycosylation regulates S protein maturation, with the underlying molecular mechanisms remaining poorly understood. Here, we demonstrate that N-glycosylation at N61/ N343 contributes to spike ER-to-Golgi trafficking. Specifically, defects in S protein's N-glycosylation (including mutations at N61 or N343, N-glycosylation inhibitors treatment, and MOGS depletion) result in ER retention through COPI-mediated retrograde Golgi-to-ER transport, and thus, the S proteins are not effectively cleaved by furin in the Golgi. This impairment of S protein maturation leads to a significant reduction in viral infectivity, which highlights the key role of N-glycosylation at residues N61 and N343 in SARS-CoV-2 life cycle. Overall, our findings uncover the molecular mechanism by which N-glycosylation controls SARS-CoV-2 spike intracellular trafficking, offering novel insights for anti-SARS-CoV-2 strategies.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0027026"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574605","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":"SADS-CoV NS3 induces apoptosis by blocking the formation of Bcl-xL-BAK complex.","authors":"Chunxiao Mou, Meiqi Liu, Yingjie Xiang, Changhua Lin, Shengbin Zhang, Kaichuang Shi, Shuping Feng, Jingyun Ma, Zhenhai Chen","doi":"10.1128/jvi.00216-26","DOIUrl":"10.1128/jvi.00216-26","url":null,"abstract":"<p><p>Swine acute diarrhea syndrome coronavirus (SADS-CoV) is an emerging porcine coronavirus with characteristics of bat origin, posing a potential threat to animal welfare and public health. Recent studies have shown that apoptosis induced by SADS-CoV contributes to virus replication. However, the virus proteins involved in SADS-CoV-induced apoptosis and their potential molecular mechanisms remain largely unknown. This study found that the SADS-CoV accessory protein NS3 interacted with the BH3 domain of Bcl-xL in the mitochondria. This interaction disrupted the Bcl-xL-BAK complex, leading to increased activation of BAK and subsequent induction of mitochondrion-mediated apoptosis. Furthermore, knockout of Bcl-xL reduced the NS3-induced apoptosis and increased the replication of SADS-CoV. Additionally, deletion of the NS3 gene decreased SADS-CoV-induced apoptosis and diminished the viral pathogenicity in murine models, indicating that NS3 is a critical determinant of SADS-CoV pathogenicity. In conclusion, our findings firstly reveal the mechanism by which SADS-CoV NS3 regulates apoptosis to enhance the viral replication and pathogenicity.<b>IMPORTANCE</b>Swine acute diarrhea syndrome coronavirus (SADS-CoV) has caused significant disruptions in porcine breeding and raised concerns regarding potential human infection. Thus far, the roles of virus proteins in virus replication and pathogenesis remain largely unknown. Here, we first investigated the functions of SADS-CoV NS3 in apoptosis and viral pathogenicity. Our findings indicated that NS3 blocked the combination of anti-apoptosis protein Bcl-xL with pro-apoptosis protein BAK, then promoting the BAK pore-forming and inducing mitochondrion-mediated apoptosis, thereby enhancing the pathogenicity of virus. Moreover, we also discovered for the first time that Bcl-xL could act as an important antiviral factor to inhibit SADS-CoV replication. These results contribute valuable insights into the novel roles of bat-borne coronavirus accessory proteins in viral replication and pathogenicity in potentially infected hosts.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0021626"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581590","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":"Potent <i>in vitro</i> synergistic antiviral effects of the pan-coronavirus fusion inhibitor EK1 in combination with RBD-specific antibodies or M^pro inhibitors.","authors":"Ruixue Xiu, Yuanzhou Wang, Wenbo Cai, Qian Wang, Minxiang Xie, Yingdan Wang, Cheng Li, Qiao Wang, Jinghe Huang, Tianlei Ying, Chuanjun Song, Lu Lu, Shibo Jiang, Wei Xu","doi":"10.1128/jvi.00076-26","DOIUrl":"10.1128/jvi.00076-26","url":null,"abstract":"<p><p>The continuous evolution of coronaviruses compromises the efficacy of existing therapeutic antibodies and replication inhibitors, necessitating antiviral strategies that are resilient to viral escape. Distinct from conventional antibody cocktails that remain vulnerable to spike protein mutations, we evaluated a multi-mechanistic therapy targeting three discrete stages of the viral life cycle: receptor binding, membrane fusion, and viral replication. Using pseudotyped and authentic human coronaviruses (HCoVs), including SARS-CoV-2 and HCoV-OC43, in cell culture models, we demonstrated that combining the pan-coronavirus fusion inhibitor EK1 with a receptor-binding domain-specific broadly neutralizing antibody (bnAb) and/or a main protease (M^pro) inhibitor yields synergistic inhibition. Collectively, our findings establish a conceptual framework for a trident antiviral regimen that theoretically restricts the evolutionary space for viral escape, although clinical translation will require optimizing delivery strategies to reconcile the distinct pharmacokinetic profiles of these agents.IMPORTANCEThe continuous emergence of highly transmissible and immune-evasive SARS-CoV-2 variants highlights an urgent need for broad-spectrum antiviral approaches capable of countering rapid viral evolution and future coronavirus outbreaks. Here, we designed a dual- or triple-stage antiviral strategy centered on the membrane fusion inhibitor EK1, in combination with a receptor-binding domain-targeting antibody and/or a small-molecule viral replication inhibitor (M^pro inhibitor). In cell culture models, our results demonstrate marked synergy between EK1 and the antibody and/or the replication inhibitor. These combinations not only enhance antiviral potency but are also anticipated to maintain efficacy against emerging variants. By targeting non-overlapping stages of the viral life cycle, this approach theoretically raises the genetic barrier to resistance. While clinical translation will require reconciling the distinct pharmacokinetic profiles of these components, our study provides a conceptual framework for developing a trident anti-coronavirus therapy.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0007626"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574678","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":"Chicken infectious anemia virus exploits host CK2α as an essential factor for its replication via VP2 Ser182/Asp183-mediated interaction.","authors":"Ziyue Ma, Hongnuan Wang, Yongqiang Wang, Xiaoqi Li, Hong Cao, Li Gao, Shijun J Zheng","doi":"10.1128/jvi.01739-25","DOIUrl":"10.1128/jvi.01739-25","url":null,"abstract":"<p><p>Chicken infectious anemia virus (CIAV) induces severe immunosuppression in chickens. The nonstructural protein VP2 of CIAV is shown to play critical roles in viral assembly and viral replication. However, the molecular mechanisms by which CIAV VP2 hijacks host machinery to promote efficient viral replication remain elusive. Here, we showed that casein kinase 2 alpha (CK2α) subunit was identified to interact with CIAV VP2 to promote viral replication. We found that knockdown of cellular CK2α by RNAi in MDCC-MSB1 or inhibition of its kinase activity by an inhibitor significantly suppressed CIAV replication in cells. Furthermore, we verified that CK2α stabilized VP2 by inhibiting its proteasomal degradation. In addition, we demonstrated that Ser182 and Asp183 of VP2 served as essential residues for CK2α binding. Using reverse genetics technique, we rescued the recombinant virus with mutations at Ser182 and Asp183 of VP2 and demonstrated that mutations at these sites disrupted VP2-CK2α binding, reduced viral replication, and mitigated CIAV-induced bone marrow hypoplasia and thymic damage <i>in vivo</i>. Our results indicate that CIAV exploits cellular CK2α for its replication and pathogenesis, implying that CK2α can be used as a potential target for the development of antiviral drugs in effective control of CIAV infection.</p><p><strong>Importance: </strong>Chicken infectious anemia virus (CIAV) causes severe immunosuppression and substantial economic losses in the global poultry industry. Current strategies to control CIAV infection are still limited. This study identifies host kinase casein kinase 2 alpha (CK2α) as a key cellular factor that binds and stabilizes CIAV VP2, promoting viral replication. Inhibition or knockdown of CK2α suppressed viral replication. The rescued virus with VP2 S182A/D183A mutations exhibited reduced viral replication and attenuated pathogenicity. These findings reveal a crucial mechanism whereby CIAV VP2 exploits host CK2α for efficient viral replication, highlighting the VP2-CK2α interaction as a potential target for developing novel antiviral strategies.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0173925"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581582","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":"Swine GBP1 restricts PDCoV replication via disrupting the replication and transcription complex formation.","authors":"Kunli Zhang, Sutian Wang, Xintong Kang, Fei Li, Ziqiao Zhao, Wuri Nile, Chunhong Zhang, Haiyan Shen, Shouwen Du, Huahua Kang, Mingfei Sun, Zhicheng Liu, Jianfeng Zhang","doi":"10.1128/jvi.00207-26","DOIUrl":"https://doi.org/10.1128/jvi.00207-26","url":null,"abstract":"<p><p>Porcine deltacoronavirus (PDCoV) has been prevalent worldwide for over a decade, causing considerable economic damage to the pig industry and posing a potential threat to public biosecurity. In this study, we found that one of the interferon-stimulated genes (ISGs), swine guanylate-binding proteins 1 (sGBP1), was induced by PDCoV. In the experiments we describe below, we demonstrate that sGBP1 is an antiviral gene inhibiting PDCoV infection by utilizing the sGBP1 stable expression cell line and sGBP1 knockout cell line. Both the large GTPase domain and the α-helical domain are responsible for sGBP1 anti-PDCoV replication. Notably, sGBP1 directly interacts with the scaffold protein NSP8 of the PDCoV replication and transcription complex (RTC). Moreover, the large GTPase domain of sGBP1 interacts with the NTD domain of NSP8, which disrupts the interaction between NSP8 and NSP12 in RTC. In addition, sGBP1 is able to bind with the RNA of PDCoV and inhibits RTC from binding with virus RNA. Here, our research uncovers a new mechanism through which sGBP1 inhibits PDCoV replication. This finding not only deepens our comprehension of the antiviral roles of ISG molecules but also offers a promising target for the prevention of PDCoV infections.IMPORTANCEPDCoV is an enteric coronavirus that has garnered significant global attention due to its current prevalence in causing diarrhea and even mortality in pigs, as well as its broad host range encompassing poultry, rodents, ruminants, and even humans. Understanding the mechanism by which host factors inhibit viral replication is critical for developing effective antiviral strategies. Here, we found that PDCoV induced swine guanylate-binding proteins 1 (sGBP1) to inhibit viral replication. Our study first reveals that sGBP1 impairs the replication and transcription complex (RTC) formation through two ways: (i) competes with the RNA-dependent RNA polymerase (RdRp) NSP12 to bind with NSP8; (ii) sGBP1 binds with PDCoV RNA to inhibit the RNA binding of RTC. Our results uncover a previously unknown antiviral mechanism of GBP1, offering a promising target for the prevention of viral infections.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0020726"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729286","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}

{"title":"Re-engineering segment 8 facilitates generation of a versatile live-attenuated influenza A virus vector platform for secretory protein delivery.","authors":"Soner Yildiz, Sara S El Zahed, Fernando Villalón-Letelier, Qian Wang, Sowmya Yelleswarapu, Gloria Dawodu, Kaijun Jiang, Raveen Rathnasinghe, Umut Karakus, Rocio Seoane, Sara Cuadrado-Castano, Adolfo García-Sastre","doi":"10.1128/jvi.00347-26","DOIUrl":"https://doi.org/10.1128/jvi.00347-26","url":null,"abstract":"<p><p>Influenza A viruses (IAVs) lacking the nonstructural protein 1 (NS1) gene (IAV-ΔNS1) are attenuated both <i>in vitro</i> and <i>in vivo,</i> yet retain replicative capacity in interferon signaling-deficient systems. To date, several efforts have been pursued to expand its functionality by incorporating transgenes in lieu of the NS1 gene. However, such vectors require complex segment designs, retain residual NS1 peptide stretches, or display suboptimal cytokine secretion, largely due to the constraints related to the partial nuclear export protein (NEP) open reading frame (ORF) upstream of the transgene integration site. Here, we describe a novel segment 8 design that can accommodate a transgene, where the complete NEP ORF is positioned downstream of the splicing acceptor site, thereby mitigating previous genetic constraints. Using this strategy, we successfully generated a recombinant IAV-ΔNS1 virus carrying the human interleukin 2 (IL-2) gene, inducing robust secretion of bioactive IL-2 upon infection. The vector demonstrated high replicative capacity, achieving titers comparable to wild-type viruses in MDCK cells expressing NS1 protein, and exhibited genetic stability over 10 successive passages. Importantly, infection induced notable viral antigen expression and high levels of bioactive IL-2 secretion in interferon-competent systems, such as MDCK, A549, and HEK293T cells <i>in vitro</i> and in mice upon pulmonary delivery <i>in vivo</i>. Furthermore, the transgene was easily swapped with a diverse array of genes encoding human IL-15, nanoluciferase, or fluorescent proteins such as miniSOG and miRFP670nano, highlighting the versatility of the platform.</p><p><strong>Importance: </strong>IAV-ΔNS1 vectors are promising vaccine platforms that elicit strong immune responses with a good safety profile. However, integration of immune-stimulatory cytokines into vector design to boost immunogenicity has been technically challenging. In this study, we developed a genetically re-engineered segment 8 design that overcomes prior limitations due to design complexity or vector efficiency, enabling high-level expression of the transgene, i.e., human interleukin 2 and other diverse proteins. The platform retains strong replicative capacity in permissive systems and remains genetically stable, making it suitable for scalable vaccine or therapeutic development. By improving both the flexibility and functionality of IAV-ΔNS1 vectors, our work advances the utility of influenza A viruses as customizable tools for vaccine delivery, immune modulation, and therapeutic applications.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0034726"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729320","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}

{"title":"Modeling human enterovirus A71 infection using an intestinal microphysiological system.","authors":"Hiroki Futatsusako, Sayaka Deguchi, Kaori Kosugi, Rina Hashimoto, Noriyo Nagata, Tadaki Suzuki, Takuya Yamamoto, Kazuo Takayama","doi":"10.1128/jvi.00250-26","DOIUrl":"https://doi.org/10.1128/jvi.00250-26","url":null,"abstract":"<p><p>Enterovirus A71 (EV-A71), a causative virus of hand, foot, and mouth disease, primarily infects and replicates in the intestine and, in severe cases, spreads to the central nervous system, leading to neurological complications. Therefore, suppressing viral replication in the intestine is important to prevent severe complications. However, the intestinal pathophysiological changes in EV-A71-infected patients remain poorly understood. In this study, we aimed to examine the intestinal response to EV-A71 infection using the intestinal microphysiological system (MPS) we previously developed using human pluripotent stem cells and microfluidic devices. The viral titers were detectable in the cell culture supernatant of the intestinal MPS for 14 days after the viral infection. Despite this, EV-A71 infection did not induce significant morphological changes in the intestinal MPS or alter the expression of epithelial cell markers, suggesting that the virus can infect the intestinal MPS without causing intestinal epithelial damage. In addition, we found that the secretion of interferons (IFNs) in the cell culture supernatant was not increased by viral infection. Interestingly, treatment with recombinant IFNs increased the expression of innate immune response-related genes and reduced viral mRNA levels. A strong association was observed between EV-A71 infection and IFN signaling in the intestinal MPS. We believe that the intestinal MPS would be a valuable platform for studying EV-A71 infection and evaluating antiviral strategies.IMPORTANCEEnterovirus A71 (EV-A71), a major cause of hand, foot, and mouth disease, primarily replicates in the intestine and can spread to the central nervous system, causing severe neurological complications. Suppressing intestinal replication is therefore critical, yet the intestinal pathophysiology of EV-A71 remains poorly understood. Here, we examined EV-A71 infection using a human pluripotent stem cell-derived intestinal microphysiological system (MPS). Viral titers were detectable in the culture supernatant for 14 days. However, EV-A71 did not induce significant morphological changes or alter epithelial marker expression, indicating persistent infection without intestinal damage. Additionally, EV-A71 infection did not enhance interferon (IFN) secretion. Treatment with recombinant IFNs increased innate immune gene expression and reduced viral mRNA, demonstrating the key role of IFN signaling in restricting infection. These findings suggest that the intestinal MPS would be a useful platform for studying EV-A71 infection and antiviral strategies.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0025026"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729333","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}

{"title":"Erratum for Li et al., \"Bispecific antibodies targeting MPXV A29 and B6 demonstrate efficacy against MPXV infection\".","authors":"Mengjun Li, Jiayin Chen, Fuxiang Wang, Jiahua Kuang, Yun Peng, Sadia Asghar, Wei Zhao, Yang Yang, Chenguang Shen","doi":"10.1128/jvi.00350-26","DOIUrl":"10.1128/jvi.00350-26","url":null,"abstract":"","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0035026"},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147468668","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}