Virology最新文献

{"title":"A high-throughput, microplate reader-based method to monitor in vitro HIV latency reversal in the absence of flow cytometry.","authors":"Chantal Emade Nkwelle, Unique Stephens, Kimberly Liang, Joel Cassel, Joseph M Salvino, Luis J Montaner, Roland N Ndip, Seraphine N Esemu, Fidele Ntie-Kang, Ian Tietjen","doi":"10.1016/j.virol.2025.110418","DOIUrl":"https://doi.org/10.1016/j.virol.2025.110418","url":null,"abstract":"<p><p>J-Lat cells are derivatives of the Jurkat CD4⁺ T cell line that contain a non-infectious, inducible HIV provirus with a GFP tag. While these cells have substantially advanced our understanding of HIV latency, their use by many laboratories in low and middle-income countries is restricted by limited access to flow cytometry. To overcome this barrier, we describe a modified J-Lat assay using a standard microplate reader that detects HIV-GFP expression following treatment with latency-reversing agents (LRAs). We show that HIV reactivation by control LRAs like prostratin and romidepsin is readily detected with dose dependence and with significant correlation and sensitivity to standard flow cytometry. For example, 10 μM prostratin induced a 20.1 ± 3.3-fold increase in GFP fluorescence in the microplate reader assay, which corresponded to 64.2 ± 5.0% GFP-positive cells detected by flow cytometery. Similarly, 0.3 μM prostratin induced a 1.7 ± 1.2-fold increase compared to 8.7 ± 5.7% GFP-positive cells detected. Using this method, we screen 79 epigenetic modifiers and identify CUDC-101, molibresib, and quisinostat as novel LRAs. This microplate reader-based method offers accessibility to researchers in resource-limited regions to work with J-Lat cells and more actively participate in global HIV cure research efforts.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"604 ","pages":"110418"},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The link between respiratory syncytial virus (RSV) morphogenesis and virus transmission: Towards a paradigm for understanding RSV transmission in the upper airway.","authors":"Richard J Sugrue, Boon Huan Tan","doi":"10.1016/j.virol.2025.110413","DOIUrl":"https://doi.org/10.1016/j.virol.2025.110413","url":null,"abstract":"<p><p>Respiratory syncytial virus (RSV) particle assembly occurs on the surface of infected cells at specialized membrane domain called lipid rafts. The mature RSV particles assemble as filamentous projections called virus filaments, and these structures form on the surface of many permissive cell types indicating that this is a robust feature of the RSV particle assembly. The virus filaments also form on nasal airway organoids systems providing evidence that these structures also have a clinical relevance. Virus filaments also form on cells infected with the closely related human metapneumovirus, suggesting that virus filament formation may be a common feature of assembly process for viruses within the Pneumoviridae family. During RSV infection these virus filaments mediate the localized cell-to-cell spread of virus infection, suggesting that they play an important role in virus transmission. The current understanding of the connection between virus filament formation and virus transmission during RSV infection is presented.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"604 ","pages":"110413"},"PeriodicalIF":0.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitination-dependent degradation of DHX36 mediated by porcine circovirus type 3 capsid protein.","authors":"Jie Zhao, Qianhong Dai, Haoyu Sun, Beiyi Zhou, Xiaoyuan Lan, Yonghui Qiu, Qianqian Zhang, Dedong Wang, Yongqiu Cui, Jinshuo Guo, Lei Hou, Jue Liu, Jianwei Zhou","doi":"10.1016/j.virol.2025.110419","DOIUrl":"https://doi.org/10.1016/j.virol.2025.110419","url":null,"abstract":"<p><p>Porcine circovirus type 3 (PCV3) is an emerging pathogen that causes porcine dermatitis, and reproductive failure. PCV3 Cap interacts with DExD/H-box helicase 36 (DHX36), a protein that functions primarily through regulating interferon (IFN)-β production. However, how the interaction between DHX36 and PCV3 Cap regulates viral replication remains unknown. Herein, we observed impaired PCV3 proliferation after DHX36 overexpression as indicated by decreased Rep protein expression and virus production. In contrast, PCV3 replication increased upon small interfering RNA-mediated DHX36 depletion. Furthermore, DHX36 positively regulated IFN-β production and interferon-stimulated genes (ISGs) expression. Mechanistically, PCV3 Cap interacted with DHX36, and the PCV3 Cap-NLS and DHX36-NTD were essential for the interaction. Furthermore, DHX36 may get degraded because its binding cellular partners became ubiquitinated and then reduced, and PCV3 Cap-(35-100aa) also promoted the degradation of DHX36 through the K48-linked ubiquitination. Taken together, these results show that DHX36 antagonizes PCV3 replication by interacting with PCV3 Cap and activating IFN-β response, which provides important insight on the prevention and controlling of PCV3 infection. IMPORTANCE: Porcine circovirus type 3 (PCV3) is a newly discovered pathogen associated with multiple clinicopathological signs. Clarifying the mechanisms that host factors modulate PCV3 replication helps understanding of the viral pathogenesis. The PCV3 capsid (Cap) protein has been shown to interact with DExD/H-box helicase 36 (DHX36) (Zhou et al., 2022b), a crucial protein that regulates virus replication. Herein, we further demonstrated that DHX36 protein is degraded in PCV3-infected cells and antagonizes the replication of PCV3 and that DHX36 increases interferon-β and interferon-stimulated gene levels by binding to PCV3 Cap. In addition, PCV3 infection could decrease DHX36 expression levels to antagonize its antiviral activity. These results reveal a molecular mechanism by which DHX36 antagonizes PCV3 replication by binding to PCV3 Cap protein and activating IFN signals, thereby providing important targets for preventing and controlling PCV3 infection.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"604 ","pages":"110419"},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Galectin-8 and GEL01 as potential adjuvants to enhance the immune response induced by a DNA vaccine against bovine alphaherpesvirus Type-1.","authors":"Claudia Alejandra Kornuta, Juan Esteban Bidart, Ivana Soria, Valeria Quattrocchi, Mariela Gammella, María Virginia Tribulatti, Oscar Campetella, Cecilia Arahí Prato, Julieta Carabelli, Felipe Andrés Cheuquepán, Yanina Paola Hecker, Prando Dadin Moore, Patricia Inés Zamorano, Cecilia Ana Langellotti","doi":"10.1016/j.virol.2025.110402","DOIUrl":"https://doi.org/10.1016/j.virol.2025.110402","url":null,"abstract":"<p><p>Bovine alphaherpesvirus-1 (BoAHV-1) causes several symptoms in cattle, leading to significant costs for the livestock industry. In this study, we used a plasmid encoding a secreted form of BoAHV-1 glycoprotein D (pCIgD) as a DNA vaccine. To enhance the potency of the pCIgD vaccine, we used Montanide™ GEL01 PR (GEL01) and introduced Galectin-8 (Gal-8), a lectin considered a novel adjuvant due to its immunostimulatory effects, into the formulation. Animals were vaccinated with pCIgD, pCIgD with Gal-8 (pCIgD-Gal-8), pCIgD with Gal-8 and GEL01 (pCIgD-Gal-8-GEL01), or the control plasmid pCIneo. The immune response was first assessed in a mouse model and then in bovines. The results showed that combining Gal-8 and GEL01 with pCIgD modulated immune responses at both the humoral and cellular levels in both animal models. This study evaluates the efficacy of a DNA vaccine with Gal-8 and GEL01 as potential adjuvants to enhance immune protection against BoAHV-1.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"604 ","pages":"110402"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards developing multistrain PEDV vaccines: Integrating basic concepts and SARS-CoV-2 pan-sarbecovirus strategies.","authors":"Mario Fragoso-Saavedra, Qiang Liu","doi":"10.1016/j.virol.2025.110412","DOIUrl":"https://doi.org/10.1016/j.virol.2025.110412","url":null,"abstract":"<p><p>Porcine epidemic diarrhea virus (PEDV) is a major pathogen impacting the global pig industry, with outbreaks causing significant financial losses. The genetic variability of PEDV has posed challenges for vaccine development since its identification in the 1970s, a problem that intensified with its global emergence in the 2010s. Since current vaccines provide limited cross-protection against PEDV strains, and the development of multistrain PEDV vaccines remains an underexplored area of research, there is an urgent need for improved vaccine solutions. The rapid development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and ongoing pan-sarbecovirus vaccine research, have demonstrated the potential of next-generation vaccine platforms and novel antigen design strategies. These advancements offer valuable insights for the development of multistrain PEDV vaccines. This review summarizes key aspects of PEDV virology and explores multistrain vaccine development considering SARS-CoV-2 vaccine innovations, proposing a framework for developing next-generation PEDV vaccine solutions.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"604 ","pages":"110412"},"PeriodicalIF":0.0,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology and genotypic diversity of duck hepatitis B virus identified from waterfowl in partial areas of Guangdong province, Southern China.","authors":"Xinyan Yao, Chaoxiang Jia, Anqi Li, Ting Qin, Dai Peng, Yingqian Han, Shuang Guo, Kai Zhong, Guoyu Yang, Yueying Wang, Heping Li","doi":"10.1016/j.virol.2025.110416","DOIUrl":"https://doi.org/10.1016/j.virol.2025.110416","url":null,"abstract":"<p><p>Duck Hepatitis B virus (DHBV) infection model is extensively utilized as an animal model for studying human hepatitis B virus infection and for comparative research. 557 liver samples from geese and ducks were collected in parts of Guangdong province, southern China. The overall prevalence of DHBV was 45.6% (254/557) in all samples. And the 27 complete genome sequences of DHBV strains in this study share 89.6%-100% genome-wide pairwise identity with previously identified DHBV genomes. Notably, DHBV-1, DHBV-2 and DHBV-3 of were found co-circulating among the waterfowl population in parts of Guangdong. More importantly, seven out of the 16 recombination events were determined involved DHBV sequences obtained in this study as major parent and minor parent, suggesting DHBV strains from Guangdong province play an important role in recombination events. Additionally, purifying selection was the dominant evolutionary pressure acting on the genomes of DHBV.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"603 ","pages":"110416"},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural insights into nucleocapsid protein variability: Implications for PJ34 efficacy against SARS-CoV-2.","authors":"Akima Yamamoto, Haruki Ito, Takemasa Sakaguchi, Akifumi Higashiura","doi":"10.1016/j.virol.2025.110411","DOIUrl":"https://doi.org/10.1016/j.virol.2025.110411","url":null,"abstract":"<p><p>Human coronaviruses (HCoVs) include common cold viruses such as HCoV-229E, OC43, NL63 and HKU1 as well as MERS-CoV and SARS-CoV, which cause severe respiratory disease. Recently, SARS-CoV-2 caused a COVID-19 pandemic. The nucleocapsid (N) protein of coronaviruses, which is essential for RNA binding and homodimerization, has a highly conserved structure across viruses. Previous studies revealed that compound PJ34 is an inhibitor of nucleic acid binding to the N-terminal domain (NTD) of the HCoV-OC43 N protein, suggesting that it could block viral replication. However, testing with SARS-CoV-2 showed that PJ34 did not inhibit viral replication. Structural analysis suggests that the substitution of Tyr for Ala at position 50 (corresponding to Tyr63 in OC43), may affect the ability to interact with compounds such as PJ34, explaining its lack of efficacy. These findings underscore the importance of structure-based drug development targeting the N protein, which remains an important therapeutic target in all coronaviruses.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"604 ","pages":"110411"},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protease activity of NIa-Pro determines systemic pathogenicity of clover yellow vein virus.","authors":"Xinjian Zhuang, Wenyi Zhang, Shuqi Xu, Wenxuan Yang, Jinlong Yin, Tong Zhou, Jiban K Kundu, Kai Xu","doi":"10.1016/j.virol.2025.110417","DOIUrl":"https://doi.org/10.1016/j.virol.2025.110417","url":null,"abstract":"<p><p>Clover yellow vein virus (ClYVV), a potyvirus that infects various dicotyledonous plants, poses a significant threat to the cultivation of legumes. Although potyviral NIa-Pro was extensively studied in viral infection cycle and host antiviral responses, the contribution of NIa-Pro protease activity to virus systemic symptoms has not yet been reported. In this study, we developed infectious clones of a ClYVV isolated from Pisum sativum. The rescued ClYVV showed robust infectivity and induced obvious systemic mosaic and necrosis symptoms in the model host Nicotiana benthamiana and natural hosts Pisum sativum and Vicia faba. Using a potato virus X (PVX) vector to express 11 ClYVV proteins in N. benthamiana ectopically, we identified that NIa-Pro is the key determinant in inducing systemic symptoms and causes higher leaf ROS levels and cell death. Further, we found that the protease-inactive mutant NIa-Pro^C151A causes significantly reduced systemic symptoms when expressed via the PVX vector and does not induce higher cellular ROS levels and cell death when transiently overexpressed compared to wild-type NIa-Pro. Overall, this study provides evidence supporting that the protease activity of a potyvirus protein NIa-Pro directly contributes to the virus symptoms.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"604 ","pages":"110417"},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethyl caffeate as a novel targeted inhibitor of 3CLpro with antiviral activity against porcine epidemic diarrhea virus.","authors":"Limin Jiang, Minghui Gu, Jiawei Xiao, Yingying Zhao, Fanbo Shen, Xingyang Guo, Hansong Li, Donghua Guo, Chunqiu Li, Qinghe Zhu, Dan Yang, Xiaoxu Xing, Dongbo Sun","doi":"10.1016/j.virol.2025.110406","DOIUrl":"https://doi.org/10.1016/j.virol.2025.110406","url":null,"abstract":"<p><p>Porcine epidemic diarrhea virus (PEDV) can cause severe diarrhea death in newborn piglets, resulting in significant economic losses for the pig industry. Therefore, the advancement of safe and effective anti-PEDV drugs for the treatment of PEDV is of paramount importance. In this study, molecular docking was used to screen natural drugs that can target PEDV 3C like protease (3CLpro). As well, the anti-PEDV effects of the screened drugs were evaluated in vitro and in vivo. Molecular docking and molecular dynamics (MD) simulation results showed that ethyl caffeate (EC) could efficiently bind to the active cavity of PEDV 3CLpro. Biolayer interferometry (BLI) and fluorescence resonance energy transfer (FRET) analyses demonstrated that EC directly interacts with PEDV 3CLpro (K_D = 1650 μM) and inhibits the activity of 3CLpro (IC₅₀ = 33.87 μM). EC has been shown to significantly inhibit the replication of PEDV in Vero E6 cells. The half maximal inhibitory concentration (CC₅₀) and half-effective concentration (EC₅₀) were determined to be 283.1 μM and 8.641 μM, respectively, yielding a selectivity index as high as 32.7. Furthermore, EC was evaluated using a piglet infection model for PEDV. It demonstrated the ability to inhibit PEDV infection in vivo and improve the survival rate of piglets (3/5, 60%). Compared to the control group, oral administration of EC significantly reduced intestinal pathological damage and viral load. Our study indicated that EC, targeting PEDV 3CLpro, is a safe and effective anti-PEDV drug with promising clinical application prospects.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"604 ","pages":"110406"},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune responses to avian influenza viruses in chickens.","authors":"Mohamed S H Hassan, Shayan Sharif","doi":"10.1016/j.virol.2025.110405","DOIUrl":"https://doi.org/10.1016/j.virol.2025.110405","url":null,"abstract":"<p><p>Chickens are a key species in both the manifestation of avian influenza and the potential for zoonotic transmission. Avian influenza virus (AIV) infection in chickens can range from asymptomatic or mild disease with low pathogenic AIVs (LPAIVs) to systemic fatal disease with high pathogenic AIVs (HPAIVs). During AIV infection in chickens, Toll-like receptor 7 and melanoma differentiation-associated gene 5 are upregulated to detect the single-stranded ribonucleic acid genomes of AIV, triggering a signaling cascade that produces interferons (IFNs) and pro-inflammatory cytokines. These inflammatory mediators induce the expression of antiviral proteins and recruit immune system cells, such as macrophages and dendritic cells, to the infection site. AIV evades these antiviral responses primarily through its non-structural protein 1, which suppresses type I IFNs, influencing viral pathogenicity. The uncontrolled release of pro-inflammatory cytokines may contribute to the pathogenicity and high mortality associated with HPAIV infections. AIV modulates apoptosis in chicken cells to enhance its replication, with variations in apoptosis pathways influenced by viral strain and host cell type. The presentation of AIV antigens to T and B cells leads to the production of neutralizing antibodies and the targeted destruction of infected cells by CD8⁺ T cells, respectively, which enhances protection and establishes immunological memory. This review explores the diverse innate and adaptive immune responses in chickens to different AIVs, focusing on the dynamics of these responses relative to protection, susceptibility, and potential immunopathology. By understanding these immune mechanisms, informed strategies for controlling AIV infection and improving chicken health can be developed.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"603 ","pages":"110405"},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}