Virology最新文献

{"title":"The combinatorial activities of oseltamivir and molnupiravir against influenza virus infections in vitro and in vivo","authors":"Xili Feng ,&nbsp;Xuanye Yang ,&nbsp;Xinyan Hu ,&nbsp;Qianyun Liu ,&nbsp;Yulin Ding ,&nbsp;Xiaoan Cao ,&nbsp;Zhongren Ma ,&nbsp;Xiaoxia Ma","doi":"10.1016/j.virol.2025.110642","DOIUrl":"10.1016/j.virol.2025.110642","url":null,"abstract":"<div><div>Oseltamivir, a neuraminidase inhibitor, is widely used in the clinic for treating influenza virus infections. However, suboptimal efficacy and risk of drug resistance development remain major challenges. Molnupiravir, a ribonucleoside analog, was originally developed to treat influenza, but was repurposed and first approved for treating COVID-19 in 2021. Considering their complementary mode-of-actions, this study aimed to investigate the combinatorial activities of oseltamivir and molnupiravir against influenza virus infections. In cell culture models, we found that β-d-N4-hydroxycytidine (NHC), the active form of molnupiravir, exerted more potent antiviral activities against influenza A and B viruses, when compared to oseltamivir treatment. Combination of NHC with oseltamivir exhibited a synergistic antiviral effect against the influenza A/Puerto Rico/8/34 H1N1 strain, but not the influenza B/Washington/02/2019 strain. In a mouse model infected with the PR/8 virus strain, treatment with molnupiravir alone or in combination with oseltamivir effectively attenuated lung injury and reduced viral load in the tissue. Taken together, molnupiravir can be explored in combination with oseltamivir to treat influenza, especially for patients infected with the oseltamivir-resistant strains, whereas further research is warranted.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"611 ","pages":"Article 110642"},"PeriodicalIF":2.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antigenic and glycan-binding characteristics of norovirus GII.20 capsid protein VP1","authors":"Xuanze Ouyang ,&nbsp;Jingdong Song ,&nbsp;Lili Li ,&nbsp;Jinsong Li ,&nbsp;Miao Jin ,&nbsp;Xiaoman Sun ,&nbsp;Zhaojun Duan","doi":"10.1016/j.virol.2025.110627","DOIUrl":"10.1016/j.virol.2025.110627","url":null,"abstract":"<div><div>Human norovirus (NoV) is one of the major pathogens causing acute gastroenteritis. The GII.20 NoV VP1 reveals a close evolutionary relationship with that of the widely prevalent GII.4 genotype based on sequence phylogenetic analysis. In this study, we characterized the antigenic properties and glycan binding profile of GII.20 VP1 protein. GII.20 VP1 protein was successfully produced using a baculovirus expression system, and self-assembled into virus-like particles (VLPs) with a diameter of approximately 38 nm. Immunological assays demonstrated that polyclonal sera generated against GII.20 VLPs exhibited strong binding activity at dilution up to 1:8,192,000, while maintaining detectable cross-reactivity with GII.4 VLP at 1:128,000. dilution. Reciprocal cross-reactivity was observed, with <em>anti</em>-GII.4 sera recognizing GII.20 VLP at 1:125,000 dilution. Blocking assays demonstrated mutual partial cross-blocking between the antisera, with half-maximal blocking dilutions of 36 (<em>anti</em>-GII.20 sera) and 297 (<em>anti</em>-GII.4). Blocking assays demonstrated mutual partial cross-blocking effects between the antisera, with half-maximal blocking dilution of 36 and 297 for <em>anti</em>-GII.20 and <em>anti</em>-GII.4 polyclonal sera, respectively. Saliva binding analysis revealed that GII.20 VLPs recognize A, B, and O blood type saliva. Sequence alignment showed conserved key amino acids in the putative glycan-binding region between GII.20 and GII.4 genotypes. Structural modeling of the GII.20 P domain revealed high similarity with the corresponding domains of both GII.17 and GII.4 NoVs. These findings establish that GII.20 VP1 shares functional characteristics with GII.4 in both glycan binding specificity and antigenic cross-reactivity, providing more insights into the molecular epidemiology of diverse NoV genotypes.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"611 ","pages":"Article 110627"},"PeriodicalIF":2.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Murine antibody 4B1D3 exhibits broad cross-reactivity and neutralizing activity against SARS-CoV-2 variants","authors":"Mariângela de Oliveira Silva ,&nbsp;Isabela Pazotti Daher ,&nbsp;Catarina Harumi Oda Ibrahim ,&nbsp;Edmarcia Elisa de Souza ,&nbsp;Edilberto Postol ,&nbsp;Raquel Elaine de Alencar ,&nbsp;Guilherme Antônio de Souza Silva ,&nbsp;Rodolfo Ferreira Marques ,&nbsp;Flávia Lopes Adami ,&nbsp;Viviane Schuch ,&nbsp;Marcio Massao Yamamoto ,&nbsp;Bianca da Silva Almeida ,&nbsp;Gabriela Koike ,&nbsp;Isabela Resende Azevedo ,&nbsp;Maria Fernanda Castro-Amarante ,&nbsp;Daniela Santoro Rosa ,&nbsp;Edison Luiz Durigon ,&nbsp;Carsten Wrenger ,&nbsp;Edecio Cunha-Neto ,&nbsp;Jorge Kalil ,&nbsp;Silvia Beatriz Boscardin","doi":"10.1016/j.virol.2025.110629","DOIUrl":"10.1016/j.virol.2025.110629","url":null,"abstract":"<div><div>The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), identified in late 2019, spurred a global pandemic, prompting an unprecedented international mobilization in vaccination and public health strategies. Although the pandemic is now under greater control, the worldwide dissemination of variants of concern (VOCs) has led to resistance and decreased vaccine efficacy, highlighting the urgent need for broad-spectrum therapeutic and preventive solutions. In this study, we employed hybridoma technology to generate monoclonal antibodies (mAbs) from mice immunized with the SARS-CoV-2 Wuhan Spike protein trimer. We selected clones producing anti-Spike receptor-binding domain (RBD) mAbs and characterized a panel of four mAbs to assess their potential as antiviral agents and their utility as tools in research and diagnostics. Our results showed that all mAbs recognized the SARS-CoV-2 Wuhan strain in infected cells through immunofluorescence assay. Moreover, the binding profiles of these mAbs against the RBD protein from various SARS-CoV-2 variants revealed distinct reactivity and loss of binding as VOCs emerged. However, one mAb, named 4B1D3, showed the most promising features, exhibiting broad binding and neutralizing capacity across all tested SARS-CoV-2 variants, including Omicron BA.2, BA.4/5 and XBB.1.5 sublineages. Furthermore, a single prophylactic dose of the 4B1D3 mAb provided protection to K18-hACE2 mice against a lethal challenge with SARS-CoV-2 Wuhan strain. In conclusion, these mAbs represent valuable tools for research and diagnostics and have significant potential for the development of new therapeutic strategies against SARS-CoV-2 variants.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"611 ","pages":"Article 110629"},"PeriodicalIF":2.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oropouche virus infection induces pyroptosis in human THP-1 macrophages","authors":"Eduardo Jurado-Cobena ,&nbsp;Cigdem Alkan ,&nbsp;Tetsuro Ikegami","doi":"10.1016/j.virol.2025.110630","DOIUrl":"10.1016/j.virol.2025.110630","url":null,"abstract":"<div><div>Oropouche fever, an emerging zoonotic viral disease in Central and South America, is caused by Oropouche virus (OROV). While typically self-limiting, severe complications such as aseptic meningoencephalitis, miscarriage, and neonatal malformations can occur. Macrophages are critical in host defense, but the pathological mechanisms underlying OROV infection remain unclear. IL-1β, a key pro-inflammatory cytokine, plays a central role in the febrile response and is regulated by inflammasomes, such as NLRP3. This study investigates NLRP3-mediated IL-1β maturation and pyroptotic cell death in OROV-infected human THP-1 macrophages. Our findings reveal that macrophages, but not monocytes, are permissive to OROV infection and undergo pyroptosis through the activation of caspases-1, -3, and -8, resulting in the cleavage of GSDMD and GSDME, and the release of IL-1β. Interestingly, the cleaved form of GSDMD was predominantly the inactive p23 fragment. Furthermore, NLRP3-deficient macrophages failed to activate caspases, cleave Gasdermins, or produce IL-1β upon infection. These results demonstrate that OROV infection triggers NLRP3-mediated IL-1β maturation and release via pyroptosis in macrophages, underscoring their potential role in OROV pathogenesis.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"611 ","pages":"Article 110630"},"PeriodicalIF":2.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The evolution and adaptation of dengue virus: Basic concepts and public health implications in Indonesia","authors":"Mohamad S. Hakim ,&nbsp;Madiha Fatima ,&nbsp;Byron Martina ,&nbsp;Marco Goeijenbier","doi":"10.1016/j.virol.2025.110628","DOIUrl":"10.1016/j.virol.2025.110628","url":null,"abstract":"<div><div>Virus mutation and evolution are inevitable, including dengue virus (DENV). In fact, for a long time up to the present day, we have been confronted with the continuous evolution of viruses, marked by the emergence of novel viruses in humans with the potential to cause epidemics and pandemics. This review aims to emphasize the fundamental concepts of virus evolution, specifically in DENV, as well as its public health impact in Indonesia. As an RNA virus, DENV continuously evolves in the face of selection pressure, including that of the host immune responses. Observing the evolution of viruses in real-time will make us better prepared to face epidemics caused by DENV. Several studies conducted in Indonesia have demonstrated that a shift in the dominance of circulating serotypes is associated with an increased number of cases, underscoring the importance of population immunity in outbreak dynamics. A major outbreak in Indonesia in 2004 was associated with a shift from DENV-2 to DENV-3. A similar phenomenon was also observed once there was a genotype shift. Additionally, phylogenetic studies indicated an association between particular genotypes and the severity of diseases. In conclusion, these studies clearly demonstrate that viral evolution can have a significant impact on public health. Advanced next-generation sequencing technologies can be utilised to detect subtle genetic changes that may be associated with the onset of epidemics.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"610 ","pages":"Article 110628"},"PeriodicalIF":2.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of synonymous codons with optimization / deoptimization in nucleoprotein (NP) gene of influenza A virus on interaction between NP and tripartite motif protein 25 (TRIM25)","authors":"Xinyan Hu ,&nbsp;Mingyang Gao ,&nbsp;Xiaoting Ren ,&nbsp;Lele An ,&nbsp;Chunlin Wang ,&nbsp;Xiao-xia Ma","doi":"10.1016/j.virol.2025.110626","DOIUrl":"10.1016/j.virol.2025.110626","url":null,"abstract":"<div><div>Nucleoprotein (NP), which performs multiple functions, participates in the life cycle of the influenza A virus (IAV). Although the synonymous codon usage of IAV NP exhibits a relatively variable pattern, it demonstrates a significant bias. Here, we first validated the directional interaction between IAV NP and tripartite motif protein 25 (TRIM25). Using the NP coding sequence of IAV PR8, we replaced all codon positions in the wild type NP coding sequence with either favorable or rare synonymous codons to construct two NP mutants: NP_optimal and NP_rare. Compared to the mRNA stability and translation efficiency of the wild type NP, both NP mutants exhibit significant impairments, particularly NP_optimal. Furthermore, in comparison to the interaction between TRIM25 and wild type IAV NP, NP_optimal completely loses this biological function, whereas NP_rare still binds to TRIM25, albeit with significant impairment. Moreover, the forward segment of IAV NP, identified as having a specific interaction with TRIM25, can be significantly impaired due to changes in synonymous codons. To some extent, these results address the question of why a strong usage bias of synonymous codons persists in the IAV <em>NP</em> gene, despite the variability in synonymous codon usage. Understanding the changes in synonymous codons that influence mRNA stability, translation speed, and folding-function provides new insights into the evolutionary mechanisms of IAV NP.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"610 ","pages":"Article 110626"},"PeriodicalIF":2.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of the COVID-19 pandemic on the molecular epidemiology of respiratory rhinoviruses and enteroviruses in Tunisia","authors":"Fahmi Smaoui ,&nbsp;Awatef Taktak ,&nbsp;Saba Gargouri ,&nbsp;Amel Chtourou ,&nbsp;Rim Kharrat ,&nbsp;Ahmed Rebai ,&nbsp;Lamia Feki-Berrajah ,&nbsp;Hela Karray-Hakim","doi":"10.1016/j.virol.2025.110624","DOIUrl":"10.1016/j.virol.2025.110624","url":null,"abstract":"<div><h3>Background</h3><div>Rhinoviruses (RVs) and enteroviruses (EVs) are major causes of respiratory infections. The COVID-19 pandemic, marked by widespread public health interventions, disrupted viral circulation worldwide. This study assessed the impact of the pandemic on the molecular epidemiology and genetic diversity of RV/EVs in Tunisia.</div></div><div><h3>Methods</h3><div>We screened 883 nasopharyngeal samples collected between October 2020 and August 2022 for RV/EVs using commercial and/or <em>in-house</em> RT-PCR assays. Sequencing was performed to identify species and genotypes. For comparison, publicly available international sequences and pre-COVID-19 Tunisian sequences were included. Maximum-likelihood phylogeny and pairwise single nucleotide polymorphism distances were used to estimate genetic relationship. Rarefaction and extrapolation analyses were conducted to assess genotype diversity.</div></div><div><h3>Results</h3><div>RV/EVs maintained circulation during the pandemic with an overall detection rate of 16.5 %. RV-A was the predominant species (47.4 %), followed by RV-C (29.5 %) and RV-B (20.5 %), EV-B and EV-D (1.3 % each). RVs exhibited high genotype diversity, with 42 observed genotypes. Intra-genotype diversity was low during the pandemic in most cases, although a genetic divergence was observed from Tunisian sequences obtained few months before the outbreak. Rarefaction and extrapolation analyses suggested that genotype diversity increased during autumn 2021–summer 2022 compared to the earlier phase of the pandemic (autumn 2020–summer 2021). However, the overall genetic diversity during the pandemic was largely comparable to pre-pandemic levels.</div></div><div><h3>Conclusion</h3><div>This study provides the first analysis of RV/EV molecular epidemiology in North Africa during the COVID-19 pandemic. The continued circulation and high genetic diversity of RVs highlight their resilience to public health measures and potential viral interference.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"610 ","pages":"Article 110624"},"PeriodicalIF":2.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Four critical epitopes of the nucleocapsid protein contribute to serological cross-reactivity between porcine epidemic diarrhea virus and porcine deltacoronavirus","authors":"Dongsheng Wang ,&nbsp;Ruiming Yu ,&nbsp;Liping Zhang ,&nbsp;Zhongwang Zhang ,&nbsp;Peng Zhou ,&nbsp;Xia Liu ,&nbsp;Huichen Guo ,&nbsp;Li Pan ,&nbsp;Xiaohua Du ,&nbsp;Xinsheng Liu","doi":"10.1016/j.virol.2025.110625","DOIUrl":"10.1016/j.virol.2025.110625","url":null,"abstract":"<div><div>Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) coronaviruses cause highly similar histopathological damage and clinical symptoms, and often appear as mixed infections in clinic, leading to great economic losses in the pig industry. Previous studies have demonstrated a certain degree of serological cross-reactivity between PDCoV and PEDV. However, the antigens and crucial epitopes contributing to serological cross-reactivity remain unclear. In this study, the specific viral antigen and crucial epitopes leading to serological cross-reactivity between PDCoV and PEDV were investigated. The nucleocapsid (N) protein was the contributing viral antigen. Truncation and mutation of the PDCoV N protein revealed that the region for serological cross-reactivity was located in the N-terminal domain. The crucial epitopes were amino acid aa19−62, aa79−91, aa102−196, and aa285−342. In addition, these crucial epitopes were highly homologous between the N proteins of PDCoV and other coronaviruses, suggesting that these sites may be the crucial epitopes inducing serological cross-reactivity between different coronaviruses. Moreover, an indirect ELISA capable of specifically differentiating PDCoV and PEDV sera was established by virtue of the C-terminal-truncated portion of N protein, which had low serological cross-reactivity. In conclusion, the main antigen and crucial epitopes leading to serological cross-reactivity between PDCoV and PEDV were identified. The specific ELISA created in this study provided important clues and effective methods for subsequent establishment of the diagnostic methods for PDCoV and PEDV, as well as effective differentiation between them in clinical practice.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"610 ","pages":"Article 110625"},"PeriodicalIF":2.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Various states of the capsid proteins released from Japanese encephalitis virus-infected cells","authors":"Sora Ohta ,&nbsp;Kotaro Ishida ,&nbsp;Simon Goto ,&nbsp;Ryuta Iwatsuki ,&nbsp;Koki Saito ,&nbsp;Eiji Morita","doi":"10.1016/j.virol.2025.110622","DOIUrl":"10.1016/j.virol.2025.110622","url":null,"abstract":"<div><div>In orthoflaviviruses, the viral capsid protein plays a crucial role in genome packaging and formation of infectious viral particles. However, their functions are believed to be diverse owing to their unique properties. In this study, we investigated the secretion of a capsid protein, independent of its role in viral particle assembly, using a recombinant Japanese encephalitis virus (JEV) expressing a capsid protein fused with a HiBiT tag (JEV C-HiBiT), a highly sensitive reporter tag. JEV C-HiBiT exhibited a growth rate similar to that of JEV WT, although the infected cells showed strong HiBiT-dependent NanoLuc luciferase activity. Sucrose density gradient fractionation analysis of the culture supernatants from JEV C-HiBiT-infected 293T cells revealed that the capsid was released in two distinct states. Studies on secondary infection and comparisons with transiently expressing cells indicated that the heavier peaks corresponded to virions, whereas the lighter peaks corresponded to free capsid proteins. Additionally, when SH-SY5Y, K562, and C6/36 cells were used as host cells, additional capsid protein peaks corresponding to subviral particles and/or membrane vesicles were detected. Treatment with Bafilomycin A1 enhanced free capsid protein secretion, and capsid proteins were localized within the lysosomes, suggesting that the free capsids were released by the lysosome-mediated secretion pathway. These findings indicate that the capsid protein is not merely a structural factor required for genome packaging but may also play multiple roles in viral propagation.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"610 ","pages":"Article 110622"},"PeriodicalIF":2.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and biological characteristics analysis of a gene-deleted recombinant virus strain of LSDV-ORF151","authors":"Jiaqi Li ,&nbsp;Qunhua Ke ,&nbsp;Weitao Huang ,&nbsp;Shanhui Ren ,&nbsp;Miaomiao Li ,&nbsp;Kaishen Yao ,&nbsp;Xiaoqin Ma ,&nbsp;Yuefeng Sun ,&nbsp;Xiangping Yin","doi":"10.1016/j.virol.2025.110623","DOIUrl":"10.1016/j.virol.2025.110623","url":null,"abstract":"<div><div>Lumpy Skin Disease (LSD), caused by the Lumpy Skin Disease Virus (LSDV), is a highly virulent infectious disease that significantly impacts cattle health and economic productivity. The mechanisms underlying LSDV virulence and immune evasion remains poorly understood, and no commercial gene-deletion attenuated vaccine is currently available. This study aims to elucidate the functional role of LSDV genes and identify potential candidate strains for vaccine development. We focused on LSDV-ORF151, a gene potentially involved in immune response and apoptosis. Through amino acid sequence analysis and protein function prediction, we hypothesized that LSDV-ORF151 modulates host immune responses. RT-qPCR results showed that LSDV-ORF151 significantly reduces IFN-β transcription levels, suggesting its role in viral immune evasion. Using homologous recombination and limited dilution techniques, we constructed and purified a recombinant LSDV strain with an ORF151 deletion, using enhanced green fluorescent protein (EGFP) as a marker. PCR amplification and sequencing confirmed the stable inheritance of the rLSDV-ΔORF151-EGFP strain over at least 20 generations. Growth curve analysis revealed a slightly lower replication capacity compared to the wild-type LSDV strain (LSDV-WT), indicating that ORF151 deletion may attenuate viral replication. RT-qPCR showed that rLSDV-ΔORF151-EGFP induces higher IFN-β transcription levels than LSDV-WT after 24 h. Transcriptomic analysis indicated that the rLSDV-ΔORF151-EGFP strain induces heightened inflammatory and immune responses, and increased apoptosis in MDBK cells compared to LSDV-WT. This study provides a promising candidate for an LSDV gene-deletion attenuated vaccine and a theoretical foundation for further exploration of LSDV-ORF151's biological functions.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"610 ","pages":"Article 110623"},"PeriodicalIF":2.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}