Journal of Virology最新文献

{"title":"Correction for Shetty et al., \"Influenza virus infection and aerosol shedding kinetics in a controlled human infection model\".","authors":"Nishit Shetty, Meredith J Shephard, Nicole C Rockey, Hollie Macenczak, Jessica Traenkner, Shamika Danzy, Nahara Vargas-Maldonado, Peter J Arts, Valerie Le Sage, Evan J Anderson, G Marshall Lyon, Eric Charles Fitts, Dalia A Gulick, Aneesh K Mehta, Mikhael F El-Chami, Colleen S Kraft, Andrew P Catchpole, Alex Mann, Krista R Wigginton, Anice C Lowen, Linsey C Marr, Nadine G Rouphael, Seema S Lakdawala","doi":"10.1128/jvi.01354-25","DOIUrl":"https://doi.org/10.1128/jvi.01354-25","url":null,"abstract":"","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0135425"},"PeriodicalIF":3.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238914","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":"Adjuvant-dependent protection of SARS-CoV-2 spike vaccines: comparative immunogenicity of human-applicable formulations.","authors":"Zhendong Pan, Liangliang Jiang, Yingying Chen, Haoran Peng, Yangang Liu, Xu Zheng, Yanhua He, Yan Liu, Ying Wang, Xiaoyan Zhang, Zhongtian Qi, Cuiling Ding, Jianqing Xu, Ping Zhao","doi":"10.1128/jvi.01099-25","DOIUrl":"https://doi.org/10.1128/jvi.01099-25","url":null,"abstract":"<p><p>Although recombinant vaccines with various adjuvant systems are widely deployed in global coronavirus disease 2019 immunization, their distinct immune profiles have not been fully elucidated. In this study, we evaluated immune responses induced by four clinically validated adjuvants-aluminum hydroxide (Al), two water-in-oil emulsions (Montanide ISA720 and ISA51), and an oil-in-water emulsion (Sepivac SWE)-formulated with the prefusion-stabilized ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer (S-2P) in mouse models. Both S-2P:ISA720 and S-2P:ISA51 elicited potent humoral immunity, including cross-neutralizing antibodies against Omicron variants, along with robust interferon gamma-producing T-cell responses in the spleen and lung. Immunization with S-2P:ISA720 conferred complete protection against lethal challenge with the ancestral virus as well as Omicron subvariants BA.5 and BF.7. In contrast, S-2P:Al and S-2P:SWE elicited substantially weaker antibody responses, undetectable T-cell immunity, and markedly reduced protective efficacy. Prime-boost immunization with S-2P:ISA720 induced sustained peak antibody titers against both homologous SARS-CoV-2 and the Omicron BA.2 subvariant, affording complete protection for up to 17 weeks post-vaccination. While a third dose of S-2P:Al following a prime-boost regimen triggered a robust increase in antibody levels, titers declined rapidly thereafter, recapitulating the decay kinetics observed after the second dose. Both ISA720 and Al formulations exhibited age-dependent declines in antibody responses and protective efficacy. Notably, aged mice displayed markedly attenuated neuroinflammatory responses following SARS-CoV-2 challenge and significantly compromised protection after adoptive transfer of immune serum. These results underscore adjuvant-specific determinants of broad and durable immunity and reveal novel age-related constraints in vaccine-induced protection against SARS-CoV-2.</p><p><strong>Importance: </strong>Persistent viral evolution, rapid waning of vaccine-induced immunity, and the heightened vulnerability of elderly populations remain major challenges for COVID-19 vaccination strategies. In this study, we systematically assessed immune responses elicited by the ancestral spike protein formulated with four distinct adjuvants in mouse models. We demonstrate that an optimized adjuvant formulation markedly enhances the magnitude and breadth of antibody responses, potentiates T-cell immunity, and rapidly induces sustained peak antibody titers against both homologous virus and Omicron variants. Vaccine-induced antibody responses were significantly attenuated in aged mice, and furthermore, both the protective efficacy of antibodies and inflammatory cytokine responses upon viral challenge were impaired in aged animals. These results provide compelling evidence that rational adjuvant selection is critical for enabling recombinant vaccines to achieve rapid-ons","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0109925"},"PeriodicalIF":3.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213093","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":"Rescue of tomato yellow leaf curl virus mutants harboring heterologous iterons through <i>in planta</i> evolution.","authors":"Khwannarin Khemsom, Ruifan Ren, Junping Han, Camila Perdoncini Carvalho, Eric Matthew Snider, Deyong Zhang, Feng Qu","doi":"10.1128/jvi.01529-25","DOIUrl":"https://doi.org/10.1128/jvi.01529-25","url":null,"abstract":"<p><p>The single-stranded, circular DNA genomes of geminiviruses contain iterated motifs of five to six nucleotides, known as iterons, upstream of the replication protein (Rep) coding region. Iterons were previously found to interact with cognate Rep in a sequence-specific manner, and the iteron-Rep interaction was needed for viral DNA replication. Nonetheless, iterons of closely related viruses often have different sequences, suggesting diversifying selection. To identify selection pressures driving iteron diversification, we constructed tomato yellow leaf curl virus (isolate SH2) mutants in which the iteron motifs were replaced with those of closely related tobacco curly shoot virus (isolate Y35). All mutants replicated in inoculated leaves of <i>Nicotiana benthamiana</i>, but some failed to spread systemically. However, the systemic movement defects were mostly rescued by <i>de novo</i> mutations. Intriguingly, these <i>de novo</i> mutations did not restore the iterons to SH2 sequences. Rather, they likely enabled viral escape from repression exerted by the heterogeneous Y35 iterons in the absence of a matching Rep. These results suggest that iterons probably act as sites of competitive binding by host-encoded transcription factors (TFs) and the cognate Rep. We further speculate that iteron-TF binding commences as soon as viral genomes enter cell nuclei, committing genome copies to Rep mRNA transcription and protein translation, but also blocking them from replication. Conversely, iteron-Rep binding would be possible only after Rep is produced and likely repels TFs from some genome copies, permitting replication initiation. Testing this model through future research should clarify the intricate evolutionary interplays between geminiviruses and their crop hosts and inform novel management strategies.</p><p><strong>Importance: </strong>Geminiviruses are important crop pathogens worldwide for which effective control measures are lacking due to an incomplete understanding of their evolutionary dynamics in infected plants. The current study focuses on a class of short sequence repeats in geminiviral genomic DNA, known as iterons, located immediately upstream of the viral gene encoding replication protein (Rep). Iterons are interesting because, although their positions and repeat patterns are conserved across all geminiviruses, their sequence identities are highly diverse. Our investigations revealed that, contrary to previous reports, the sequence identity of iterons is non-essential for tomato yellow leaf curl virus replication. Rather, they are repressors of replication, and this repression is overcome by their binding with cognate Rep. Future investigations will likely unveil novel targets for more effective management of crop diseases caused by geminiviruses.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0152925"},"PeriodicalIF":3.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206857","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":"Tankyrases positively regulate influenza A virus replication via type I interferon response.","authors":"Gayan Bamunuarachchi, Kishore Vaddadi, Yurong Liang, Zhengyu Zhu, Quanjin Dang, Sankha Hewawasam, Lin Liu","doi":"10.1128/jvi.01298-25","DOIUrl":"https://doi.org/10.1128/jvi.01298-25","url":null,"abstract":"<p><p>Influenza viruses are respiratory pathogens that cause both seasonal and unpredictable pandemic infections in humans. Currently approved anti-influenza drugs target the viral proteins. A recurrent mutation in the influenza genome leads to drug resistance and thus hinders the efficacy of anti-influenza drug treatments. Influenza A virus (IAV) depends on host factors to complete its virus life cycle. Thus, there are increasing interests in antiviral drugs that target host cellular proteins required for virus replication. Poly (ADP-ribose) polymerases (PARPs) are the host factors that modify protein functions by adding ADP-ribose to target proteins. Using the CRISPR activation system, we screened all 17 PARP members for its effects on IAV infection in lung epithelial A549 cells. Tankyrase 1 and 2 (TNKS 1/2 or PARP5A/5B) were found to be potent proviral factors. Knockout of TNKS1 or TNKS2 in HEK293T cells by CRISPR reduced viral mRNA and protein levels in cells and viral titers in culture media. Double knockout of TNKS1 and TNKS2 had a larger effect on IAV infection than single knockout of each isoform. The effect of TNKS double knockout on IAV replication was strain independent. Overexpression of TNKS1/2 in the double knockout cells restored the IAV replication to a level similar to the control cells. TNKS double knockout activated JNK/c-Jun signaling, enhanced Stat signaling, and increased type I interferon expression. Finally, <i>Tnks1</i> or <i>Tnks2</i> KO mice challenged with a sublethal IAV showed increased type I IFN response and reduced viral load in the lungs. The survival rate of <i>Tnks1</i> or <i>Tnks2</i> KO mice from a lethal IAV infection was significantly increased compared to wild-type mice. In conclusion, TNKS1 and TNKS2 regulate influenza virus infection via type I interferon response.IMPORTANCEPoly (ADP-ribose) polymerases (PARPs) play a crucial role in DNA repair, cellular stress responses, epigenetics, gene transcription, and viral infections. However, the specific roles of PARPs in influenza A virus (IAV) infection remain unclear. In this study, we identified Tankyrase 1 and 2 (TNKS1/2 or PARP5a/5b) as the potent proviral factors. Knockout of TNKS1 or TNKS2 reduced viral replication <i>in vitro</i>, with the double knockout showing an even greater effect. TNKS double knockout also resulted in an increased type I interferon response to IAV infection. <i>In vivo</i>, Tnks1 or Tnks2 KO mice exhibited lower viral loads and higher survival rates following IAV challenge. Our findings highlight TNKS1/2 as important regulators of IAV infection and potential targets for antiviral therapies.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0129825"},"PeriodicalIF":3.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206919","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":"The E3 ubiquitin ligase STUB1 inhibits Senecavirus A replication by mediating VP1 ubiquitination and proteasomal degradation.","authors":"Penghui Zeng, Jingyu Mao, Jinshuo Guo, Xiaoyu Yang, Yongyan Shi, Xiaoyu Wang, Jiangwei Song, Jianwei Zhou, Lei Hou, Jue Liu","doi":"10.1128/jvi.01152-25","DOIUrl":"https://doi.org/10.1128/jvi.01152-25","url":null,"abstract":"<p><p>Senecavirus A (SVA), an emerging vesicular pathogen, poses a significant threat to the global pig industry. STIP1 homology and U-box-containing protein 1 (STUB1), a chaperone-dependent E3 ubiquitin ligase, plays a pivotal role in protein quality control by mediating target protein degradation. However, its precise role of STUB1 in regulating SVA replication remains undefined. In this study, we combined liquid chromatography-mass spectrometry, confocal imaging, and Western blotting to demonstrate that STUB1 interacts with the SVA VP1 protein and negatively regulates SVA replication. Mechanistically, STUB1 promotes the ubiquitination-dependent degradation of VP1 by specifically targeting lysine residues at positions 177 and 260 (K177 and K260). This degradation process is significantly enhanced by heat shock protein 70 (HSP70) and heat shock cognate protein 70 (HSC70), which strengthen the STUB1-VP1 interaction. Notably, the SVA 3C protease (3Cpro) counteracts this antiviral defense by enzymatically reducing STUB1 expression. <i>In vivo</i> studies using a mouse model showed that a VP1 mutant virus lacking STUB1-targeted ubiquitination sites replicates more efficiently than the wild-type strain, resulting in significantly higher viral loads across multiple tissues and more severe pulmonary pathology. Together, these findings reveal that STUB1 inhibits SVA replication through ubiquitination-dependent degradation of VP1, a process that is antagonized by viral 3C protease via suppression of STUB1 expression.</p><p><strong>Importance: </strong>Viruses have evolved diverse strategies to enhance their replication efficiency. Senecavirus A (SVA), an emerging porcine pathogen associated with vesicular disease outbreaks, has become increasingly prevalent in swine populations worldwide. As a chaperone-dependent E3 ubiquitin ligase, STUB1 plays a crucial role in maintaining cellular protein homeostasis. In this study, we elucidated the functional interplay between STUB1 and SVA replication. Our results demonstrate that STUB1 directly interacts with the viral protein VP1 and mediates its ubiquitination-dependent degradation through specific targeting of lysine residues at positions 177 and 260 (K177 and K260), thereby significantly inhibiting viral replication. However, SVA has evolved a countermeasure, whereby its 3C protease (3Cpro) downregulates STUB1 expression, effectively blocking VP1 degradation and subverting this host antiviral defense to promote viral propagation. These findings not only reveal novel host-virus interaction mechanisms but also provide valuable molecular targets for developing innovative strategies to control SVA infection.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0115225"},"PeriodicalIF":3.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199986","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":"Intracellular iron positively modulates the replicative cycle of mimiviruses, increasing virus production.","authors":"Juliana Dos Santos Oliveira, Claudia F Dick, Gabriel Henrique Pereira Nunes, Victor Alejandro Essus, Jason Schrad, Sundharraman Subramanian, Jônatas Abrahão, José Roberto Meyer-Fernandes, Kristin Parent, Juliana Reis Cortines","doi":"10.1128/jvi.01025-25","DOIUrl":"https://doi.org/10.1128/jvi.01025-25","url":null,"abstract":"<p><p>Mimiviruses, members of the <i>Nucleocytoviricota</i> phylum, produce large, pseudo-icosahedral virions densely coated with fibrils, except at a specialized fivefold vertex known as the stargate. Stargate opening is essential for delivering the viral core into the cytoplasm of phagocytic amoebae. These professional phagocytes deploy antimicrobial mechanisms such as the modulation of transition metal concentrations within phagolysosomes to eliminate internalized pathogens. Yet, mimiviruses have evolved striking adaptations to resist such hostile environments and initiate replication within these compartments. Here, we investigated the role of metal ions-particularly iron-in the replication of three giant viruses: <i>Acanthamoeba polyphaga mimivirus</i> (APMV), Antarctica virus, and Tupanvirus (TPV). We show that infection by these viruses increases cellular iron uptake and that elevated intracellular iron enhances viral replication. These findings reveal a previously underappreciated facet of the mimivirus-host interaction, in which iron availability acts as a positive modulator of the viral replicative cycle.IMPORTANCEGiant viruses like Mimivirus infect amoebae, which normally destroy microbes using toxic conditions inside cellular compartments. This study shows that, instead of being harmed, these viruses benefit from one of those supposedly hostile factors: iron. Through this work, we discovered that infection by Mimivirus and related viruses increases the host cell's iron uptake-and that more iron boosts virus production by the host cell. This reveals a surprising twist in the virus-host relationship: what should be a defense mechanism is turned into an advantage by the virus. By highlighting iron as a key factor in viral success, this work opens new perspectives on how giant viruses adapt to-and even exploit-the internal environment of their hosts. It also adds an important piece to our understanding of the complex strategies viruses use to survive and thrive inside cells.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0102525"},"PeriodicalIF":3.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200026","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":"Epigenetic motifs distinguishing endogenous from exogenous retroviral integrants.","authors":"Sarah LaMere, Hanbei Xiong, Wei Wang, Brian LaMere, Niema Moshiri","doi":"10.1128/jvi.00775-25","DOIUrl":"10.1128/jvi.00775-25","url":null,"abstract":"<p><p>Retroviruses are subject to epigenetic regulation by the host genome after integrating, similar to vertebrate genes. However, their patterns of integration, and therefore their likely epigenetic regulation, differ between genera. Beta- and gammaretroviruses are two types of simple retroviruses that have a strong tendency to infect germ cells and endogenize. While ancient endogenous retroviruses are often easy to spot due to mutations rendering them non-functional, more recent integrants can maintain the capacity for full viral production, making it sometimes difficult to discern which integrants are exogenous and likely more clinically relevant. Because endogenous retroviruses generally spend a longer time integrated and subject to host epigenetic regulation as proviral DNA, we hypothesized we could show these integrants exhibit sequence differences from their exogenous counterparts, likely resulting from DNA methylation and histone modifications, and that endogenous retroviruses would generally show habituation to host promoters. Therefore, we have used statistical analyses of publicly available sequence data to demonstrate that endogenous retroviral variants exhibit decreased CpG dinucleotide and altered trinucleotide frequencies over time, and that they will show evidence for loss of motifs associated with \"active\" histone modifications. Close examination of these patterns provides further clues for distinguishing endogenous and exogenous retroviral variants, potentially aiding in the study of retroviruses in less well-characterized wildlife species.</p><p><strong>Importance: </strong>Expression of vertebrate genes is regulated by chemical modifications made directly to the DNA or to the proteins associated with it, termed epigenetics. Because retroviruses integrate into DNA, they are subject to the same epigenetic modifications as regular genes. Retroviruses will tend to endogenize, meaning they will become a permanent part of a species' genome when their hidden DNA is passed down to progeny during reproduction. However, sometimes it is difficult to discern whether a retroviral sequence is endogenous (permanently fixed) or exogenous (an infectious entity). We hypothesized that changes to the retroviral sequences over time after endogenization would result from epigenetic modifications, and that these changes could help distinguish an endogenous retrovirus from an exogenous one. In this paper, we show that changes to the viral sequences associated with epigenetics indeed take place after endogenization.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0077525"},"PeriodicalIF":3.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192021","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":"Identification of viral activators of the HSV-2 UL13 protein kinase.","authors":"Naoto Koyanagi, Kosuke Takeshima, Saori Shio, Yuhei Maruzuru, Akihisa Kato, Yasushi Kawaguchi","doi":"10.1128/jvi.01165-25","DOIUrl":"https://doi.org/10.1128/jvi.01165-25","url":null,"abstract":"<p><p>Although previous studies reported that the herpes simplex virus 2 (HSV-2) UL13 protein kinase mediates the phosphorylation of elongation factor 1δ (EF-1δ) in infected cells, we found here that individual expression of UL13 was insufficient to induce phosphorylation of EF-1δ in mammalian cells. This led us to hypothesize that HSV-2 UL13 requires viral cofactors for full kinase activity and prompted us to identify such cofactors. Our results were as follows. (i) Co-expression of UL13 with UL55 or Us10 significantly enhanced phosphorylation of EF-1δ compared to UL13 alone. (ii) UL13 was co-precipitated with UL55 or Us10 upon co-expression, and its kinase activity was significantly increased in their presence, as demonstrated by <i>in vitro</i> kinase assays. (iii) In HSV-2-infected cells, UL13 was co-precipitated with Us10 and UL55. (iv) The UL55-null mutation significantly reduced phosphorylation of EF-1δ in HSV-2-infected cells, whereas the Us10-null mutation had little effect; however, the double-null mutation further decreased the phosphorylation compared to the UL55-null mutation alone. (v) The UL55-null mutation, but not the Us10-null mutation, significantly reduced HSV-2 replication and cell-cell spread in U2OS cells to levels comparable to those observed with the UL13 kinase-dead mutation. These results suggest that UL55 acts as a principal activator of UL13 in HSV-2-infected cells, whereas Us10 serves as an auxiliary activator. Moreover, the role of UL13 kinase activity in HSV-2 replication and cell-cell spread in U2OS cells appears to be largely dependent on UL55.IMPORTANCEHerpesviruses encode conserved protein kinases (CHPKs) that often target cellular cyclin-dependent kinase (CDK) phosphorylation sites. CHPKs from beta- and gammaherpesviruses can exhibit these CDK-like functions even when individually expressed in mammalian cells. In contrast, CHPKs from alphaherpesviruses display these CDK-like functions in infected cells, but not upon individual expression, suggesting that they require additional viral factors to exhibit full kinase activity. In this study, we focused on HSV-2 UL13, an alphaherpesvirus CHPK, and identified HSV-2 UL55 and Us10 as viral activators of UL13. In HSV-2-infected cells, UL55 functions as a principal activator of UL13, while Us10 serves as an auxiliary activator. Importantly, the contribution of UL13 kinase activity to HSV-2 replication and cell-cell spread appears to be largely dependent on the presence of UL55. Our findings uncover a previously unrecognized mechanism of CHPK regulation in alphaherpesviruses and provide new insights into the evolutionary diversification of viral kinase control.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0116525"},"PeriodicalIF":3.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192058","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":"Correction for Zhao et al., \"IDO1 promotes CSFV replication by mediating tryptophan metabolism to inhibit NF-κB signaling\".","authors":"Feifan Zhao, Yaoyao Huang, Junzhi Ji, Xueyi Liu, Xiaowen Li, Linke Zou, Keke Wu, Xiao di Liu, Sen Zeng, Xinyan Wang, Wenshuo Hu, Yiwan Song, Zhimin Lu, Bolun Zhou, Peng Li, Weijun Wang, Mingqiu Zhao, Jinding Chen, Lin Yi, Shuangqi Fan","doi":"10.1128/jvi.01094-25","DOIUrl":"https://doi.org/10.1128/jvi.01094-25","url":null,"abstract":"","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0109425"},"PeriodicalIF":3.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191980","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":"HIV proviral transcription and infectivity are enhanced by neddylation.","authors":"Cristina C Vaca, Hannah Hudson, Isabelle Clerc, Chisu Song, Richard T D'Aquila","doi":"10.1128/jvi.00968-25","DOIUrl":"https://doi.org/10.1128/jvi.00968-25","url":null,"abstract":"<p><p>A spreading infection can quickly restart from the persistent reservoir of cells harboring HIV proviruses if antiretroviral therapy (ART) is stopped. HIV transcription can also be increased by latency-reversing agents (LRAs) during ART. Neddylation is a post-translational modification that activates Cullin-RING ligases (CRLs), which ubiquitinate several proteins that regulate HIV transcription and infectivity, marking these regulators for proteasomal degradation. We studied how inhibiting neddylation affects HIV gene expression <i>ex vivo</i> after three LRAs: TNFα, PMA and ionomycin, and JQ1. In provirus-containing T cells, broad inhibition of CRL-mediated ubiquitination using MLN4924 (MLN) with the above LRAs reduced HIV transcriptional initiation, decreased virus production, and diminished virion infectivity by increasing A3G incorporation. Decreased degradation of inhibitor of kB alpha (IkBα) was implicated in reducing LRA-stimulated HIV transcription. MLN also decreased HIV reactivation after PMA and ionomycin treatment of CD4+ T cells from ART-suppressed people living with HIV. Results indicate that neddylation can enhance HIV proviral transcription and reactivated virion infectivity.IMPORTANCEResults indicate that neddylation contributes to reactivating HIV provirus transcription and antigen expression, as well as enhancing infectivity of resulting virions. This suggests hypotheses to test in the future that may inform a novel strategy for research to enable antiretroviral therapy (ART)-free remission of HIV infection, including whether inhibiting neddylation when ART stops reduces spontaneous provirus reactivation and increases virus A3G content to help control HIV rebound from latent reservoirs post-ART.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0096825"},"PeriodicalIF":3.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192074","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}