Journal of Virology最新文献

{"title":"Dairy cattle herds mount a characteristic antibody response to highly pathogenic H5N1 avian influenza viruses.","authors":"Lindsey R Robinson-McCarthy, Holly C Simmons, Aaron L Graber, Carly N Marble, Grace W Graudin, Kevin R McCarthy","doi":"10.1128/jvi.00621-25","DOIUrl":"10.1128/jvi.00621-25","url":null,"abstract":"<p><p>An unprecedented outbreak of a highly pathogenic avian influenza virus, H5 clade 2.3.4.4b, was reported in U.S. dairy cattle during the spring of 2024. It has now spread to hundreds of herds across multiple states. In humans, antibodies to the hemagglutinin (HA) protein confer the strongest protection against infection. Human herd immunity limits viral spread but also drives the emergence of antigenic variants that escape dominant antibody responses. We used store-bought milk to profile the collective H5N1 antibody response of dairy cattle herds. We detected HA binding antibodies in specific samples from states with recent/ongoing outbreaks. These antibodies present in milk neutralized replicating virus expressing dairy cattle HA and neuraminidase (NA). Despite originating from independent vendors, dairies/plants, geographic regions, and time, antibodies present in these samples are remarkably similar in activity and HA binding specificity. The dominant antibody response was clade 2.3.4.4b HA specific, followed by cross-reactivity with other H5s. Whether the uniformity of the response is a pathway to achieve herd immunity or an avenue for antigenic variants to rapidly escape remains to be seen.IMPORTANCEEstablishing human herd immunity ends pandemics. For influenza viruses, this immunity drives continued antigenic evolution that enables viruses to infect once-immune individuals. An outbreak of highly pathogenic avian influenza virus was detected in dairy cattle in 2024 and has spread rapidly across herds and states. We report approaches to assess dairy cattle herd immunity using store-bought milk samples. Across samples separated by geography and time, we find dairy cattle mount a strikingly similar antibody response that is strongest to the dairy cattle virus. Benchmarking immunity at this phase of the outbreak is important to understand either eradication or the emergence of antigenic variants that enable reinfection.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0062125"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959012","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 attenuated African swine fever virus with deletions of the <i>CD2v</i> and <i>A137R</i> genes offers complete protection against homologous challenge in pigs.","authors":"Guorui Peng, Xin Zhao, Xingqi Zou, He Zhang, Junjie Zhao, Xuezhi Zuo, Shuguang Tan, Ruizhi Wu, Xue Guan, Shihua Li, Yuan Xu, Yingju Xia, Xiaoai Xu, Lu Xu, Yuanyuan Zhu, Jinhua Liu, Yebing Liu, George Fu Gao","doi":"10.1128/jvi.00262-25","DOIUrl":"10.1128/jvi.00262-25","url":null,"abstract":"<p><p>African swine fever (ASF) has caused a devastating pandemic among domestic and wild swine, leading to significant economic losses in the global swine industry. Recombinant live-attenuated vaccines are a potential option for the control of ASF. However, safe and effective vaccines against the ASF virus (ASFV) are not yet commercially available, and thus, additional vaccine candidates still need to be developed. In this study, we demonstrate that the simultaneous deletion of the ASFV genes <i>CD2v</i> and <i>A137R</i> from the highly virulent isolate ASFV HuB/HH/2019 substantially attenuated the virulence in swine. All pigs (4/4) infected with 10⁵ TCID₅₀ doses of the double gene deletion virus HuB/HH/2019Δ<i>CD2v</i>Δ<i>A137R</i> (HuBΔ<i>CD2v</i>Δ<i>A137R</i>) remained healthy during a 27-day observation period, with no fevers (>40.5°C) observed. Cases of viremia were mild and cleared by 24 days post-inoculation (dpi). Antibodies against ASFV p30 were induced, and the inoculated pigs were well-protected against homologous challenges. All inoculated pigs survived after being challenged with 10² HAD₅₀ ASFV HuB/HH/2019, and no fever or clinical symptoms developed during the 22-day monitoring period. In contrast, all control group pigs died before 11 dpi (2/2). Cytokine assays and RNA sequencing revealed mild responses elicited by HuBΔ<i>CD2v</i>Δ<i>A137R</i>. Successful innate and passive immune responses were also triggered. The findings suggest that deletion of the <i>CD2v</i> and <i>A137R</i> genes can attenuate ASFV, and the deletion mutant virus HuBΔ<i>CD2v</i>Δ<i>A137R</i> is a promising vaccine candidate.IMPORTANCEThe emergence of ASF has caused substantial economic losses in the global pig industry. In light of this, the development of a safe and effective vaccine is crucial to control the spread of ASF. In this study, a live-attenuated ASFV strain was developed by simultaneously knocking out the viral genes <i>CD2v</i> and <i>A137R</i>. The mutant virus exhibited weakened virulence in pigs, elicited robust humoral and cellular immunity, and conferred protection upon challenge with high doses of the parental virus. Notably, no fever or clinical symptoms were observed during a 27-day monitoring period. Consequently, our research presents a highly promising candidate strain for a live-attenuated vaccine, offering a significant step forward in the quest for effective prevention measures. Additionally, the identification of these specific gene targets opens up avenues for further exploration and refinement of strategies aimed at combating ASF outbreaks.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0026225"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959013","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":"SFTSV utilizes AXL/GAS6 for entry via PI3K-PLC-dependent macropinocytosis activated by AXL-kinase.","authors":"Zecheng Jin, Shuhei Taguwa, Junki Hirano, Kentaro Uemura, Chikako Ono, Akatsuki Saito, Tamaki Okabayashi, Yusuke Maeda, Taroh Kinoshita, Yoshiharu Matsuura","doi":"10.1128/jvi.00221-25","DOIUrl":"10.1128/jvi.00221-25","url":null,"abstract":"<p><p>Severe fever with thrombocytopenia syndrome (SFTS) is a significant public health concern caused by SFTS virus (SFTSV), a tick-borne RNA virus. Previous studies have identified DC-SIGN and related C-type lectins as receptors of SFTSV infection in specific cell populations. Our genome-wide CRISPR activation screening identified AXL, a receptor tyrosine kinase, as a novel entry receptor for SFTSV. We found that AXL-mediated SFTSV infection utilizes the bridging action of growth arrest-specific protein 6 between AXL and phosphatidylserine on virus particles. This interaction induces autophosphorylation of tyrosine residues in the intracellular domain of AXL, recruiting phosphatidylinositol-3 kinase (PI3K) and phospholipase C (PLC) and establishing a macropinocytotic pathway of SFTSV entry. The AXL-PI3K-PLC-dependent entry pathway was observed in diverse cell types, including human umbilical vein endothelial cells (HUVEC), offering deep insights into the lifecycle of SFTSV and offering AXL as a novel therapeutic target against SFTS.IMPORTANCEUnderstanding the molecular mechanisms of viral entry is critical for developing targeted antiviral therapies since there is no effective vaccine or antiviral drug against severe fever with thrombocytopenia syndrome (SFTS). This study uncovered AXL as a potential entry receptor for SFTS virus (SFTSV) via PI3K/PLC-dependent macropinocytosis pathway distinct from previously reported viral entry mechanism. The inhibition of these cellular enzymes resulted in the suppression of SFTSV infection in the AXL-expressing cell lines and HUVEC. Our research sheds light on the intricate molecular mechanisms underlying these interactions by utilizing mutants of AXL and represents a promising target for the development of innovative therapeutics against SFTS.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0022125"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959269","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":"Mucosal vaccination with long-form TSLP induces migratory cDC1-mediated adaptive immunity against SARS-CoV-2 infection.","authors":"Jing Hu, Housheng Zheng, Wei Ran, Xuefei Wang, Chenghui Liao, Jian Zhou, Liang Ye","doi":"10.1128/jvi.01231-25","DOIUrl":"10.1128/jvi.01231-25","url":null,"abstract":"<p><p>A combination of vaccination strategies will potentially be required for effective control of the virus pandemic. We report that mice intranasally immunized with commercial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit vaccines enriched with the human thymic stromal lymphopoietin (TSLP) variant, long-form TSLP (lfTSLP), but not the short-isoform TSLP (sfTSLP), induced robust antigen-specific systemic and mucosal antibody production. The adjuvant-enhancing activity of lfTSLP in mice requires functional TSLP receptor signals in migratory type 1 conventional dendritic cells (cDC1s). Furthermore, lfTSLP acts on migratory cDC1s to enhance T follicular helper (Tfh) cell and germinal center (GC) B cell responses. Intranasal vaccination with lfTSLP elicits long-lasting immunogenicity and protection against the challenge of wild-type SARS-CoV-2 and the B.1.617.2 variant in mice. Our study provides insights into the adjuvant role of lfTSLP, which is critical in enhancing migratory cDC1-mediated GC responses to improve vaccine efficacy.</p><p><strong>Importance: </strong>Adjuvants are indispensable components of subunit vaccines, and the development of adjuvants capable of inducing powerful systemic and mucosal immune responses is critical for enhancing the efficacy of viral vaccines. This study reveals that the human long-form thymic stromal lymphopoietin (lfTSLP) induces antigen-specific systemic IgG and mucosal IgA antibody production with sustained immunogenicity. Mechanistically, lfTSLP enhances germinal center reactions by preferentially activating migratory type 1 conventional dendritic cells (cDC1s). These findings uncover a previously unrecognized mechanism underlying the adjuvant activity of lfTSLP, which enhances vaccine-induced adaptive immunity and confers protection against SARS-CoV-2 infection. These findings indicate that the application of lfTSLP as an adjuvant should be encouraged in the rational design and development of viral vaccines.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0123125"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873853","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":"Contemporary seasonal human coronaviruses display differences in cellular tropism compared to laboratory-adapted reference strains.","authors":"Matthew J Gartner, Monique L Smith, Clyde Dapat, Yi Wen Liaw, Thomas Tran, Randy Suryadinata, Joseph Chen, Guizhi Sun, Rory A Shepherd, George Taiaroa, Michael Roche, Wen Shi Lee, Philip Robinson, Jose M Polo, Kanta Subbarao, Jessica A Neil","doi":"10.1128/jvi.00684-25","DOIUrl":"10.1128/jvi.00684-25","url":null,"abstract":"<p><p>Seasonal human coronaviruses (sHCoVs) cause 15%-30% of common colds. The reference strains used for research were isolated decades ago and have been passaged extensively, but contemporary sHCoVs have been challenging to study as they are notoriously difficult to grow in standard immortalized cell lines. Here, we addressed these issues by utilizing primary human nasal epithelial cells (HNECs) and immortalized human bronchial epithelial cells (BCi) differentiated at an air-liquid interface, as well as human embryonic stem cell-derived alveolar type II (AT2) cells to recover contemporary sHCoVs from human nasopharyngeal specimens. From 21 specimens, we recovered four HCoV-229e, three HCoV-NL63, and eight HCoV-OC43 viruses. All contemporary sHCoVs showed sequence differences from lab-adapted CoVs, particularly within the spike gene. Evidence of nucleotide changes in the receptor binding domains within HCoV-229e and detection of recombination for both HCoV-229e and HCoV-OC43 isolates was also observed. Importantly, we developed methods for the amplification of high-titer stocks of HCoV-NL63 and HCoV-229e that maintained sequence identity, and we established methods for the titration of contemporary sHCoV isolates. Comparison of lab-adapted and contemporary strains in immortalized cell lines and airway epithelial cells revealed differences in cell tropism, growth kinetics, and cytokine production between lab-adapted and contemporary sHCoV strains. These data confirm that contemporary sHCoVs differ from lab-adapted reference strains and, using the methods established here, should be used for the study of CoV biology and evaluation of medical countermeasures.IMPORTANCEZoonotic coronaviruses have caused significant public health emergencies. The occurrence of a similar spillover event in the future is likely, and efforts to further understand coronavirus biology should be a high priority. Several seasonal coronaviruses circulate within the human population. Efforts to study these viruses have been limited to reference strains isolated decades ago due to the difficulty in isolating clinical isolates. Here, we use human airway and alveolar epithelial cultures to recover contemporary isolates of human coronaviruses HCoV-NL63, HCoV-229e, and HCoV-OC43. We establish methods to make high-titer stocks and titrate HCoV-229e and HCoV-NL63 isolates. We show that contemporary isolates of HCoV-NL63 and HCoV-OC43 have a different tropism within the respiratory epithelium compared to lab-adapted strains. Although HCoV-229e clinical and lab-adapted strains similarly infect the respiratory epithelium, differences in host response and replication kinetics are observed. Using the methods developed here, future research should include contemporary isolates when studying coronavirus biology.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0068425"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144958983","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 African swine fever virus-specific antibody reactome reveals antigens as potential candidates for vaccine development.","authors":"Songxin Guo, Yi Ru, Hui Zhang, Junbiao Xue, Huanan Liu, Dong Men, Zongqiang Cui, Chaochao Shen, Hong Tian, Chun Ma, Jun Gong, Jintian Xu, Dianbing Wang, Rui Gong, Xiaowei Zhang, Heng Rong, Yan-Yi Wang, Chenli Liu, Zhuojun Dai, Shengce Tao, Jiaoyu Deng, Haixue Zheng, Feng Li, Xian-En Zhang","doi":"10.1128/jvi.00478-25","DOIUrl":"10.1128/jvi.00478-25","url":null,"abstract":"<p><p>Developing an efficient and safe vaccine for African swine fever (ASF), a devastating disease of pigs, remains a significant challenge mainly due to limited knowledge of the immune correlates of protection. Identifying protective determinants is difficult because ASF virus (ASFV) is a large and complex DNA virus encoding over 160 proteins. Here, we constructed an ASFV proteome microarray containing 160 full-length proteins for profiling ASFV-specific antibodies. An antibody reactome containing 46 ASFV proteins (including 12 newly recognized B-cell antigens) was established by analyzing several cohorts of serum samples from pigs protected with different live-attenuated vaccines (LAVs). A proteome-wide study of antibody dynamics over a 26-day period provided a multi-dimensional landscape of the host humoral response against ASFV after acute infection, LAV immunization, and post-vaccination challenge. This study provides a comprehensive understanding of ASFV-induced humoral immune responses, highlights B-cell antigen candidates for vaccine design, supports the investigation of LAV protection mechanisms, and would accelerate vaccine development.IMPORTANCEAfrican swine fever (ASF) poses a severe threat to global swine industries, with vaccine development hindered by limited understanding of immune protection. A comprehensive understanding of antibody responses against ASF virus (ASFV) and the discovery of protective antigens are fundamental to vaccine development. This study constructed an ASFV proteome microarray to profile antibody responses against 160 viral proteins and established the antibody spectra against ASFV with dynamic features. The proteome microarray offers a high-throughput platform for understanding ASFV immunology and pathogenicity and will contribute to ASF vaccine development and diagnosis.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0047825"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855692","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":"<i>N</i>-linked glycans on the stalk of influenza virus neuraminidase promote functional tetramer formation by compensating for local hydrophobicity.","authors":"Soma Saeidi, Hongquan Wan, Hyeog Kang, Jin Gao, Wells W Wu, Tahir Malik, Robert Daniels","doi":"10.1128/jvi.00879-25","DOIUrl":"10.1128/jvi.00879-25","url":null,"abstract":"<p><p>Enveloped virus surface antigens, such as influenza neuraminidase (NA), typically depend on <i>N-</i>linked glycans for assembly, trafficking in the host cell, and immune evasion. Here, we examined the function of the <i>N-</i>linked glycans on the NA stalk from H1N1 2009 pandemic (pdm09) viruses using reverse genetics coupled with a recombinant NA (rNA) analysis. Our results with the NA from A/Brisbane/02/2018 (H1N1) show that all five glycosylation sites in the stalk generally receive an <i>N-</i>linked glycan and that viral growth is largely unaffected by removing any of these sites individually. In contrast, viral growth decreased when we sequentially removed the stalk glycosylation sites, consistent with the observation that H1N1 pdm09 strains predominantly possess four or five stalk glycan sites in NA. Upon passage, the growth of the virus lacking the five stalk glycan sites significantly increased, and multiple substitutions were found that decreased the hydrophobicity near each mutated site. Reverse genetics experiments confirmed the polar stalk substitutions significantly improved viral growth and revealed an increase in the amount of NA dissociated from the virus, suggesting the stalk glycans or the hydrophobic regions protect against proteolysis. The polar substitutions also rescued the expression of a secreted recombinant NA (rNA) lacking the stalk glycan sites and significantly increased production of enzymatically active rNA that exceeded the wild-type version. These findings demonstrate that the stalk glycans promote functional NA tetramer formation by compensating for local hydrophobicity and that viral-based studies can be leveraged in the rational design of rNA antigens.IMPORTANCE<i>N-</i>linked glycans can play critical roles in viral glycoprotein maturation and immune evasion. The influenza virus glycoprotein neuraminidase (NA) possesses multiple <i>N-</i>linked glycan sites in the enzymatic head domain and stalk region that tether it to the viral surface. This study demonstrates that the stalk <i>N-</i>linked glycans contribute to viral fitness by compensating for local hydrophobicity to enable functional NA tetramer formation. Supporting this conclusion, our results show that sequential removal of the stalk glycan sites on a NA from a recent H1N1 strain leads to decreased viral growth that rapidly recovers following passage. The increased growth coincided with stalk mutations that reduced the hydrophobicity around the stalk glycan sites. We observed similar results with a secreted recombinant NA (rNA), and the amount of functional rNA produced with the polar substitutions exceeded the wild-type rNA, illustrating how viral-based studies can assist with the rational design of rNA antigens.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0087925"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873769","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":"Discovery, phylogenetic, and comparative genomic analysis of novel avian gammacoronaviruses identified in feral pigeons (<i>Columba livia domestica</i>).","authors":"Mohamed E El Zowalaty, Louis J Taylor, Yongwoo Son, Heesu Lee, Adam M Rubrum, Richard J Webby, Stephen A Bustin, Sean G Young, Sun-Hak Lee, Dong-Hun Lee, Matthew B Frieman","doi":"10.1128/jvi.01112-25","DOIUrl":"10.1128/jvi.01112-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The COVID-19 pandemic caused by SARS-CoV-2 has intensified efforts to identify emerging coronaviruses (CoVs) across diverse hosts. Spillover events, where CoVs transition from wildlife reservoirs to other species, can lead to infections with varying clinical outcomes, emphasizing the need for continued surveillance. Understanding the diversity and distribution of both known and novel CoVs in wildlife reservoirs is crucial for predicting and preventing future spillover events. In this study, we employed Illumina's Pan-CoV library panel and next-generation sequencing (NGS) to identify five novel avian-associated gammacoronavirus genomes from cloacal and oropharyngeal swabs of clinically healthy feral pigeons captured in Durban, KwaZulu-Natal Province, South Africa, in 2018. The genome sequences, ranging from 27,582 to 27,611 nucleotides, clustered with gammacoronaviruses in phylogenetic analyses but formed a distinct clade. Comparative analysis of the five conserved domains in the ORF1ab coding sequence with other gammacoronaviruses revealed Pairwise Patristic Distances (PPD) that exceeded both species and subgenus demarcation cutoffs. These findings highlight the critical need for ongoing surveillance to enhance understanding of CoV diversity, host range, and potential for cross-species transmission, aligning with One Health principles. Based on these results, we propose &lt;i&gt;Gammacoronavirus columbae&lt;/i&gt; as a new species for these pigeon gammacoronaviruses that clusters with the recently reported duck gammacoronaviruses to form a novel subgenus within Gammacoronavirus.IMPORTANCEAlthough coronaviruses are significant pathogens affecting a wide range of hosts, surveillance efforts have predominantly focused on wild mammals, leaving the diversity of avian coronaviruses largely underexplored. Here, we report the detection of novel gammacoronaviruses from feral pigeons in South Africa and propose revisions to the current taxonomic classification of Gammacoronavirus based on genetic distance analyses. These findings highlight the potential role of wild birds in the dissemination of novel coronaviruses, analogous to their established involvement in the transmission of avian influenza viruses. Our study also highlights the utility of next-generation sequencing (NGS) technologies in uncovering the hidden diversity of viruses in wildlife populations. Finally, this study reinforces the need for ongoing surveillance, continued vigilance, and further research into avian coronaviruses. The ongoing highly pathogenic avian influenza (HPAI) outbreaks in the USA have demonstrated the devastating impact of emerging avian viruses on wildlife, agriculture, and public health. Given the unpredictability of coronavirus evolution, failing to monitor their diversity and potential for cross-species transmission risks leaving us unprepared for future outbreaks. This study reinforces the urgent need for proactive, large-scale genomic surveillance of wildlife reservoirs t","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0111225"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959010","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":"New insights into temperature-impacted mycovirus-fungus interactions regulated by a microRNA in <i>Lentinula edodes</i>.","authors":"Chun-Xi Liu, Meng-Pei Guo, Jun-Zhuo Zhou, Yi-Jia Sun, Yin-Bing Bian, Zhang-Yi Xu","doi":"10.1128/jvi.00084-25","DOIUrl":"10.1128/jvi.00084-25","url":null,"abstract":"<p><p>The onset of symptoms in virus-infected mushrooms merits investigation. In this study, the influence of heat stress (HS) on the interaction between <i>Lentinula edodes</i> mycovirus HKB (LeV) and its mushroom host, <i>Lentinula edodes</i>, was explored, revealing that HS treatment facilitated LeV replication and compromised the host's thermotolerance at full growth of mycelia. Transcriptomic analysis showed that fewer genes responded to HS, and thermotolerance-related genes were downregulated when the virus infection occurred. A host microRNA, led-milR-21, proven as a negative regulator of the growth rate, thermotolerance, and resistance against <i>Trichoderma atroviride</i> of <i>L. edodes</i> mycelia by functional analyses, could be induced by both LeV infection and HS. Tobacco transient expression experiments with qRT-PCR confirmation demonstrated that led-milR-21 targeted a thermotolerance-related transcription factor <i>LE01Gene01783</i>. Further analysis showed that genes associated with tryptophan metabolism, arginine and proline metabolism, valine/leucine and isoleucine degradation, protein processing in the endoplasmic reticulum, fatty acid degradation, and glycerolipid metabolism may play roles in the responses of <i>L. edodes</i> to LeV infection and HS. Based on these findings, a putative mechanism was proposed to elucidate the interplay among temperature, LeV, and <i>L. edodes</i>. This study deepens our understanding of how fruit body-forming fungi respond to viral infection and abiotic stress, providing insights into potential virus-host interactions in a scenario of global warming.IMPORTANCEThis is the first report of a fungal miRNA being induced by a mycovirus. In <i>Lentinula edodes</i>, upon LeV infection under heat stress, LeV replication surges, triggering degradation of the LeV genome by <i>DCL1</i>, particularly on its 5'-UTR end and ORF1 upstream regions. <i>DCL1</i> and several other RNAi key genes (such as <i>LeAGO8</i>, <i>LeRDR1</i>, <i>LeRDR5</i>, and <i>LeRDR6</i>) are also possibly recruited during the thermotolerance-related host microRNA (<i>led-milR-21</i>) formation, leading to its increased production. Consequently, led-milR-21-dependent silencing of <i>LE01Gene01783</i> occurs upon LeV infection, diminishing the heat repair capacity. This study deepens our understanding of how fruiting body-forming fungi respond to viral infection and abiotic stress, providing insights into potential virus-host interactions in a scenario of global warming.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0008425"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959216","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":"Interferon-induced miR-7705 modulates the anti-virus activity of cholesterol 25-hydroxylase.","authors":"Le Wang, Hongxiao Song, Fengchao Xu, Yujia Zhu, Mian Huang, Jing Xu, Xiaolu Li, Fei Wang, Fan Yang, Yang Lei, Pujun Gao, Guangyun Tan","doi":"10.1128/jvi.01198-25","DOIUrl":"10.1128/jvi.01198-25","url":null,"abstract":"<p><p>Cholesterol 25-hydroxylase (CH25H), an interferon-stimulated gene (ISG), has been implicated in broad-spectrum antiviral immunity. Here, we identify CH25H as a potent suppressor of hepatitis B virus (HBV) replication that significantly outperforms IFN-α in reducing HBV DNA, pregenomic RNA (pgRNA), HBsAg, and HBeAg, without inducing cytotoxicity. However, CH25H is weakly expressed in hepatocytes and only modestly induced by type I interferon. We found that CH25H expression is tightly controlled by microRNAs, especially miR-7705, which is induced by IFN-α in a STAT1-dependent manner. miR-7705 directly targets the 3'UTR of CH25H, suppressing its expression and enhancing HBV replication. Knockdown of miR-7705 restores CH25H levels, enhances IFN-induced antiviral responses, and suppresses HBV replication in both transient transfection and infection models. Mechanistically, miR-7705 overexpression nullifies CH25H-mediated suppression of HBV, whereas this effect is abolished in CH25H-knockout cells, confirming the specificity of the miR-7705-CH25H axis. Furthermore, we demonstrate that this regulatory axis also governs CH25H-mediated restriction of RNA viruses, including EV71 and CVB3, suggesting its broad antiviral relevance. Importantly, antagonizing miR-7705 enhances the efficacy of IFN-based therapy against both DNA and RNA viruses. These findings reveal miR-7705 as a negative regulator of CH25H and position the miR-7705-CH25H axis as a promising target to improve antiviral immunity.</p><p><strong>Importance: </strong>This study highlights the critical role of miR-7705 in regulating the antiviral effects of interferon (IFN) therapy, particularly in the context of chronic HBV infection. By identifying miR-7705 as a key modulator of CH25H, a protein essential for controlling HBV replication, our research provides new insights into the mechanisms that limit the effectiveness of IFN treatment. Targeting miR-7705 could improve the efficacy of IFN-based therapies, offering a potential strategy to better manage HBV and other viral infections. This research paves the way for developing adjunctive treatments that enhance the body's natural antiviral responses.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0119825"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030026","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}