Journal of Virology最新文献

{"title":"Co-infection of <i>Helicobacter pylori</i> with Epstein-Barr virus in gastric organoids enhances cell proliferation and morphogenesis.","authors":"Lina Liu, Caixia Zhu, Shuxin Zhang, Yantao Duan, Yulin Zhang, Shujuan Du, Yuping Jia, Fang Wei, Daizhou Zhang, Dazhi Xu, Yuyan Wang, Qiliang Cai","doi":"10.1128/jvi.00928-25","DOIUrl":"10.1128/jvi.00928-25","url":null,"abstract":"<p><p><i>Helicobacter pylori</i> (<i>H. pylori</i>) is a key cause of chronic inflammation and gastric cancer, and Epstein-Barr virus (EBV) also contributes to gastric tumorigenesis. However, the role of EBV co-infection in <i>H. pylori</i>-related cancers remains unclear because of the lack of efficient <i>ex vivo</i> models. Organoids, which are derived from self-renewing stem cells, closely mimic <i>in situ</i> tissue structure and function, making them ideal for disease modeling. Here, we developed patient-derived normal gastric organoids (NGOs) and used high-accuracy microinjection to introduce EBV and <i>H. pylori</i> (NCTC11637 strain). We found that the co-infection of <i>H. pylori</i> and EBV induced a significant structural change and upregulated the expression of <i>TFF1</i>, <i>VIL1</i>, and <i>Lgr5</i> to promote cell proliferation and tissue morphogenesis. Analysis of transmission electron microscopy revealed an increase of <i>H. pylori</i> internal location in NGOs after co-infection. Moreover, all tested <i>H. pylori</i> strains isolated from patients displayed similar toxicities when co-infected with EBV. These findings provide a fundamental basis for evaluating pathogen toxicity, predicting disease progression, and advancing the clinical treatment of gastric cancer.</p><p><strong>Importance: </strong><i>Helicobacter pylori</i> (<i>H. pylori</i>) infection is a major contributor to chronic inflammation and the development of gastric cancer. Furthermore, Epstein-Barr virus (EBV) has been shown to play a role in the oncogenic process of gastric cancer by promoting chronic inflammation and increasing tissue damage. However, the mechanism by which co-infection contributes to gastric carcinogenesis remains unclear. In this study, we used patient-derived gastric organoids as a model to establish EBV-<i>H. pylori</i> co-infection using microinjection technology and found that co-infection causes significant structural changes and promotes cell proliferation. This model will not only contribute to a better understanding of the pathogenesis of gastric cancer but will also be important for drug efficacy evaluation and the development of new therapeutic approaches.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0092825"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959019","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":"Organoids: physiologically relevant <i>ex vivo</i> models for viral disease research.","authors":"Yijing Wang, Dingkun Peng, Meilin Li, Meng Yao, Tianlong Li, Su Li, Hua-Ji Qiu, Lian-Feng Li","doi":"10.1128/jvi.01132-25","DOIUrl":"10.1128/jvi.01132-25","url":null,"abstract":"<p><p>Viral diseases pose serious threats to human health, resulting in substantial economic losses. However, traditional disease models often fail to capture the full complexity of viral pathogenesis. Pluripotent and tissue stem cell-derived organoids help bridge this gap by closely mimicking the structure and function of native organs, thereby enabling new breakthroughs in studying viral pathogenesis. This review discusses the diverse applications of organoid models in virology, including infection modeling, host-virus interaction studies, CRISPR/Cas9-based gene editing, antiviral drug screening, and vaccine development. Here, we focus on human organoid models used to investigate viral infections, covering systemic viral infections (exemplified by viruses such as SARS-CoV-2, Zika virus, influenza virus, and monkeypox virus) as well as localized viral infections (exemplified by viruses including respiratory syncytial virus, herpes simplex virus 1, rotavirus, norovirus, hepatobiliary viruses, and cytomegalovirus). By advancing mechanistic insights and accelerating therapeutic discovery, organoid technology shows significant potential as a complementary tool for combating viral diseases.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0113225"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959246","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":"An RGD motif on SARS-CoV-2 Spike induces TGF-β signaling and downregulates interferon.","authors":"Nicholas P Gracie, Anupriya Aggarwal, Rachel Luo, Mitchell Spicer, Sobia Idrees, Caroline L Ashley, Sibel Alca, Timothy Ison, Megan C Steain, Karishma Patel, Rezwan Siddiquee, Jason K K Low, Joel P Mackay, Christopher E Denes, G Gregory Neely, Alen Faiz, Stuart G Turville, Timothy P Newsome","doi":"10.1128/jvi.00435-25","DOIUrl":"10.1128/jvi.00435-25","url":null,"abstract":"<p><p>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates canonical cell entry via ACE2 and has also been implicated as an activator of a diverse range of signaling pathways. Here, we present evidence that the RGD (Arg-Gly-Asp) motif within the receptor-binding domain (RBD) of the S1 fragment of the S protein induces TGF-β cytokine expression. RGD peptides are well characterized as ligands for a subset of integrin complexes primarily containing α5 and αV subunits. In this study, we investigate the molecular basis of TGF-β pathway activation by S protein, delivered to cells as recombinant protein, in pseudotyped virus or in virally infected cells. Activation of TGF-β signaling by the S protein requires ACE2 and leads to SMAD3-dependent expression of the pro-fibrotic marker PAI-1. Utilizing pseudotyped viruses, expression of the S protein with a mutated RGD motif abolished TGF-β signaling, as did the RGD antagonist ATN-161, implicating integrin complexes in mediating this response. We show that the S protein RGD motif suppresses IFN-β expression via TGF-β, leading to a disruption in cellular antiviral defenses, consistent with TGF-β's role in immunosuppression. These findings further support the multifunctionality of S protein and provide mechanistic insights into its activity as a virulence factor during infection.</p><p><strong>Importance: </strong>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an ongoing public health challenge as a cause of acute illness and post-acute sequelae of COVID-19 (PASC, or long COVID). Our study identifies the RGD integrin-binding motif in the spike (S) protein as central to the cellular response to SARS-CoV-2, leading to the expression of the pleiotropic cytokine TGF-β and disabling of antiviral immunity. This work further supports the S protein-to-integrin complex signaling axis as a potential therapeutic target. The RGD motif might also be a valid target for treating PASC given the increasing body of evidence implicating the presence of persistent S protein in the etiology of this disease.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0043525"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992906","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":"Inflammatory, transcriptomic, and cell fate responses underlying the mammalian transmission of avian influenza viruses.","authors":"Mark Zanin, Timothy Flerlage, Sook-San Wong, Peter Vogel, Kristine Piza, Patrick Schreiner, Zhongshan Cheng, David F Boyd, Rabeh El-Shesheny, Jeremy C Jones, Ti-Cheng Chang, Paul Thomas, Robert Webster, Richard Webby","doi":"10.1128/jvi.00647-25","DOIUrl":"10.1128/jvi.00647-25","url":null,"abstract":"<p><p>Airborne transmissibility of avian influenza viruses (AIVs) in humans is considered an essential component of their pandemic risk. Although several viral factors regulating airborne transmission (AT) have been delineated, it is not known what, if any, responses at the respiratory epithelia are determinants of AIV AT. Using responses in the ferret nasal epithelium to a panel of H1N1 AIVs, we describe host responses that segregate with AT phenotypes. AIV infection upregulated interferon alpha and gamma responses and IL-6 JAK-STAT signaling and downregulated oxidative phosphorylation. Single-cell transcriptomics revealed that cellular genotoxic stress and NF-kB, interferon, and cell fate pathways differentiated host responses to AIVs with different transmissibilities. These responses culminated in greater AIV antigen-containing exudate and debris in the respiratory spaces of the nasal epithelium of ferrets inoculated with AT AIVs. More abundant CMPK2, SP100, and CXCL10 transcription in infected epithelia was a hallmark of AT viruses. Overall, our study reveals host responses associated with AIV infection and transmission in the nasal epithelium, the determinant anatomical site of influenza virus transmission.IMPORTANCEAirborne transmission (AT) is a critical component of the pandemic risks posed by avian influenza A viruses (AIVs). However, the host responses ultimately dictating transmissibility elicited by AIVs in the upper respiratory tract of mammals, the determinant site of influenza virus AT, are largely unknown. We identified host responses in the nasal epithelium of the upper respiratory tract differentially expressed in response to infection by AIVs of different mammalian ATs. Our data indicate that a definable host response was associated with AT of AIVs. These data would serve as an important basis for future mechanistic studies of AIV zoonosis and potentially have implications for understanding the mechanisms of transmission of respiratory viruses between humans.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0064725"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799509","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":"A novel nanoparticle vaccine, based on S1-CTD, elicits robust protective immune responses against porcine deltacoronavirus.","authors":"Qing He, Yawen Zou, Beilei Yu, Qian Yuan, Chenguang Meng, Chenxuan Du, Zhiyong Wang, Jiahao Lian, Shile Luo, Siyu Cao, Wenbing Yang, Dantong Li, Hongyu Lei, Yang Zhan, Wenfeng Zhou, Yi Yang, Naidong Wang","doi":"10.1128/jvi.00674-25","DOIUrl":"10.1128/jvi.00674-25","url":null,"abstract":"<p><p>Porcine deltacoronavirus (PDCoV), an emerging swine pathogen causing severe enteric disease in piglets, poses cross-species transmission risks, including humans. The C-terminal domain (CTD) of its spike protein harbors a key receptor-binding region with antigenic specificity and cross-protective potential. Here, we developed a novel nanoparticle-based CTD vaccine (CTDnps) by conjugating PDCoV S1-CTD to bacteriophage AP205 capsids, leveraging subunit vaccine advantages in safety, scalability, and affordability, to address urgent needs for PDCoV control. Compared to the CTD monomer, the CTDnps vaccine induced a markedly faster antigen-specific IgG response and greater neutralizing antibody (NAb) titers in mice. In immunized sows, the CTDnps vaccine elicited sustained IgG and secretory IgA (sIgA) responses, with serum NAbs persisting up to 60 days post-farrowing at titers exceeding 1:64. Passive transfer of maternal antibodies to newborn piglets significantly reduced viral loads and clinical signs upon PDCoV challenge, whereas histopathological and immunohistochemical analyses confirmed reduced viral presence and intestinal damage in the CTDnps-vaccinated group. Furthermore, CTDnps enhanced dendritic cell antigen uptake and upregulated expression of major histocompatibility complex II and co-stimulatory molecules (CD80 and CD86) to activate humoral and cellular immunity. We concluded that the PDCoV S1-CTD nanoparticle vaccine has much potential for robust and prolonged PDCoV prevention. Finally, the formed nanoparticle platform has potentially broad applications for developing multivalent vaccines against diverse coronaviruses.</p><p><strong>Importance: </strong>Although porcine deltacoronavirus (PDCoV) poses a potential threat to public health, effective vaccines against PDCoV remain lacking. Here, we developed a novel nanoparticle-based C-terminal domain vaccine (CTDnps) targeting the conserved S1-CTD domain of the PDCoV spike protein. Unlike traditional subunit vaccines, CTDnps displayed AP205 capsids to enhance antigen presentation, induced rapid and robust neutralizing antibodies in sows, and conferred passive immunity to piglets via maternal antibody transfer. Mechanistically, CTDnps promoted dendritic cell activation and cellular immunity by upregulating major histocompatibility complex II and co-stimulatory molecules, a feature absent in monomeric CTD vaccines. We not only established CTDnps as a potent PDCoV intervention, but also pioneered a scalable, fast platform adaptable to emerging or multivalent coronavirus vaccines. This study provided actionable strategies to mitigate PDCoV outbreaks and broader coronavirus threats.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0067425"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959001","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":"Camptothecin, a topoisomerase I inhibitor, impedes productive herpes simplex virus type 1 infection.","authors":"Joseph R Heath, Alison E Lloyd, Raegen M Kulinski, Daniel P Fromuth, Jill A Dembowski","doi":"10.1128/jvi.01276-25","DOIUrl":"10.1128/jvi.01276-25","url":null,"abstract":"<p><p>Herpes simplex virus type 1 (HSV-1) is a double-stranded DNA virus that infects most of the human population. We previously found that cellular topoisomerase I (TOP1) associates with the HSV-1 genome throughout infection. TOP1 relieves topological stress on DNA to enable and regulate transcription, DNA replication, and DNA repair. We hypothesized that TOP1 contributes to these key viral processes because HSV-1 does not encode a topoisomerase. We found that TOP1 inhibition with camptothecin (CPT) or β-Lapachone results in a significant reduction in viral yield. The effects of CPT are reversible and occur in a dose-dependent manner, independent of strain and cell type. CPT treatment results in a decrease in viral gene expression and DNA replication, with replication defects observed at all concentrations tested. Defects in viral gene expression are not restricted to a specific gene class. However, the timing and extent of the observed defects are dose dependent. We also demonstrate that if CPT is added to cells after the onset of viral DNA replication, subsequent rounds of replication are inhibited, indicating that the replication defect observed is not simply the result of prior steps in the infectious cycle being blocked. Together, these results demonstrate that CPT is a potent inhibitor of HSV-1 infection, supporting the hypothesis that TOP1 is active on HSV-1 genomes during infection.IMPORTANCEHSV-1 is a common human pathogen. It utilizes both viral and cellular factors to facilitate infection. We previously characterized the proteins that associate with HSV-1 DNA throughout infection. One of these proteins, which has been largely unexplored in the context of HSV-1 infection, is TOP1. TOP1 functions to relieve topological stress to regulate transcription, DNA replication, and other processes that involve DNA cleavage and unwinding. Our findings support a role for TOP1 in HSV-1 DNA replication and gene expression and highlight the potential to target TOP1 activity or interactions for antiviral therapy.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0127625"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959069","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":"Parallel evolution of the elite neutralizer phenotype in divergent HIV-1 clades.","authors":"Kathryn A Mesa, Sophia W Li, Jennie M Hutchinson, Sara O'Rourke, David L Alexander, Bin Yu, Xiaoying Shen, Terri Wrin, Christos J Petropoulos, Phillip W Berman, Grant H Pogson","doi":"10.1128/jvi.00433-25","DOIUrl":"10.1128/jvi.00433-25","url":null,"abstract":"<p><p>The development of an effective vaccine against HIV-1 requires understanding how broadly neutralizing antibodies (bNAbs) evolve in natural viral infections. Here, we recovered 152 envelope sequences from two elite neutralizers (ENs) and five viral controllers and determined the neutralization sensitivity (IC₅₀) of each envelope glycoprotein (Env) to broadly neutralizing monoclonal antibodies (bN-mAbs). For the combined EN/controller data set, we observed that the median IC₅₀ value for a CD4-binding site (CD4bs) bN-mAb (VRC01) was significantly lower for viruses lacking an N465 glycan. For a clade AE EN viral population, Env mutations implicating a VRC01-like antibody occurred in concert with positive selection at N465. Using rabbit immunizations, N465 was found to shield immunogenic VRC01 contacts in the V5/β24 domain. In the clade B EN viral population, positive selection was observed at N332, a CD4bs epitope, and a 2G12-like glycan-dependent epitope (N295-N339-N392). In rabbit immunizations, a recombinant antigen derived from the basal virus showed a greater median positivity response to cladal consensus peptides overlapping N332 than from a later virus. However, the latter virus, which displayed an N49 glycan, elicited a greater median response to consensus peptides overlapping a VRC01 contact in the C1 domain. Rarely observed C1 glycans (N49, N97) evolved in both EN viral populations. Signals of positive selection, while largely absent for glycan polymorphism present in the controllers, were detected at glycans shielding bNAb epitope contacts in both EN viral populations. Positive selection of shielding glycans suggested constraints on the escape pathways of glycan-dependent antibodies imposed by bNAb responses.<b>IMPORTANCE</b>In a small subset of HIV-1-infected individuals, natural viral evolution leads to the appearance of antibodies capable of neutralizing a broad assemblage of viruses from divergent clades (bNAbs). In this study, we determined that two viral populations with divergent infections exhibited commonalities in glycan evolution that accompanied the acquisition of exceptional serum neutralization breadth. Positive selection of glycans shielding immunogenic bNAb epitope contacts suggested conflicts for escape from glycan-dependent antibodies, and rare C1 glycan introductions highlighted the immunogenicity of a region overlapping a VRC01 epitope contact. Conflicts for glycan loss could lead to their persistence in a viral population. However, a heightening of a regional cross-reactive immune response concomitant with extraordinary glycosylation pointed to evolution of specific sequence for expanding antibody neutralization breadth. These results suggest that antigens displaying immunogenic bNAb epitopes in combination with rare glycosylation might help realize the production of an effective vaccine.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0043325"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959271","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":"Crimean-Congo hemorrhagic fever virus Africa 1 lineage in <i>Hyalomma</i> species ticks, Tunisia, 2024.","authors":"Silvia Fabi, Giuseppe Di Pietra, Elisabetta Valente, Massimo Bellato, Chiara Agostini, Michele Paccagnella, Elisa Franchin, Valentina Chisu, Cipriano Foxi, Claudia Del Vecchio, Ignazio Castagliuolo, Giovanna Masala, Cristiano Salata","doi":"10.1128/jvi.01401-25","DOIUrl":"https://doi.org/10.1128/jvi.01401-25","url":null,"abstract":"","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0140125"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124972","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":"Zika virus infection in neonatal mice disrupts connexin 43 and induces cardiac inflammation, implicating viral myocarditis in neonatal pathogenesis.","authors":"Shuxuan Li, Wangheng Hou, Najealicka Armstrong, Huan Zhao, Ruth Cruz-Cosme, Hongwei Yang, Jianhua Xu, Hongyu Chen, Chunlian Zhong, Wenkun Fu, Wei Wang, Rui Zhu, Ningshao Xia, Tong Cheng, Qiyi Tang","doi":"10.1128/jvi.00871-25","DOIUrl":"10.1128/jvi.00871-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Zika virus (ZIKV) is primarily transmitted through mosquito bites and, occasionally, via breast milk, making postnatal ZIKV infections common among newborns and infants, particularly in tropical regions. Previous studies, including ours, have demonstrated that neonatal ZIKV infection can be fatal, highlighting a severe health issue of ZIKV in newborns. However, the pathogenesis and functional outcomes of postnatal ZIKV infection remain largely unexplored. The mechanisms underlying organ failure in infected neonates are still unknown. Here, we investigated postnatal ZIKV (PRVABC59) infection in neonatal mice and found significant cardiac abnormalities. Electrocardiogram (EKG) analysis revealed extended P-R intervals (indicative of the atrioventricular block), widened QRS complexes (suggesting intraventricular block), and elevated ST wave (a biomarker of myocardium impairment), implying defects in myocardial conduction. In addition, ZIKV infection caused increased levels of cTnT, cTnI, CK, CK-MB, CCL2, CXCL9, and CXCL10-biomarkers associated with cardiovascular diseases and infarction-like myocardial pathology. To further elucidate the underlying mechanisms, we analyzed cytokine and chemokine responses and observed a significant increase in multiple inflammatory mediators, including M-CSF, LIF, IL-6, IL-15, CCL2, CCL4, CCL5, CCL11, CXCL1, CXCL9, CXCL10, TNF-α, and VEGF. Notably, ZIKV infection also led to the degradation of connexin 43 (Cx43), a critical protein involved in heart development and intercellular communication among myocardial cells. In summary, our neonatal mouse model of ZIKV infection suggests that ZIKV-induced myocarditis and cardiac dysfunction may contribute to fatal outcomes in newborns. These findings provide new insights into ZIKV pathogenesis and underscore the need for further research into its impact on the cardiovascular system in early life.IMPORTANCEZika virus (ZIKV) is a known teratogen responsible for microcephaly in neonates born to mothers infected during pregnancy. Mouse models have been instrumental in elucidating ZIKV pathogenesis; however, most published studies utilize interferon (IFN)-compromised animals, either genetically modified or antibody-treated. In this study, we employed immunocompetent neonatal mice to investigate postnatal ZIKV infection and uncovered its impact on heart function. We detected high viral loads in heart tissue at early, middle, and late stages of infection using RT-qPCR. Electrocardiogram (EKG) analysis demonstrated cardiac dysfunction, including conduction abnormalities. At the same time, elevated levels of cTnT, cTnI, CK, CK-MB, LDH, α-HBDH, CCL2, and CXCL10-hallmarks of cardiovascular pathology-suggested inflammatory responses associated with heart failure. These findings indicate that neonatal mortality following postnatal ZIKV infection may be driven by virus-induced cardiac dysfunction. Our results provide new insights into ZIKV pathogenesis, suggesting that postnatal ZIKV ","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0087125"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784561","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":"Mpox: disease manifestations and therapeutic development.","authors":"Yining Wang, Xin Wang, Tunca Doğan, Nadia A Sam-Agudu, Jaffar A Al-Tawfiq, Qiuwei Pan","doi":"10.1128/jvi.00152-25","DOIUrl":"10.1128/jvi.00152-25","url":null,"abstract":"<p><p>Mpox, caused by monkeypox virus (MPXV) infection, has emerged as a significant global health threat. The World Health Organization (WHO) has twice declared a Public Health Emergency of International Concern for mpox: first for the 2022-2023 global outbreak and subsequently for concurrent outbreaks in Africa. Beyond MPXV, other members of the Orthopoxvirus genus also pose growing risks of zoonotic spillover, with the potential to jump from animal reservoirs to humans. Clinically, mpox is distinguished from other Orthopoxvirus infections by its propensity to cause severe systemic manifestations alongside localized skin lesions, disproportionately affecting vulnerable groups such as children, pregnant women, and immunocompromised individuals. Although vaccines are available, effective therapeutics are equally essential in combating the mpox crisis. Current antiviral agents, including tecovirimat and brincidofovir, have demonstrated uncertain or disappointing efficacy in preclinical and clinical studies, underscoring the urgent need for further therapeutic development. This review provides a concise synthesis of recent advances in understanding mpox epidemiology and clinical features and offers an in-depth discussion of the current status and future directions in therapeutic development. We highlight the importance of innovative experimental models that can authentically replicate mpox disease manifestations and serve as robust platforms for therapeutic testing. Advancing these research efforts is critical for responding to the ongoing mpox emergency and for sustaining preparedness against future poxvirus epidemics.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0015225"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817039","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}