Journal of General Virology最新文献

Targeting pseudoknots with Cas13b inhibits porcine epidemic diarrhoea virus replication.

IF 3.6 4区医学

Journal of General Virology Pub Date : 2025-02-01 DOI: 10.1099/jgv.0.002071

Hee-Jeong Han, Daseuli Yu, Jeonghye Yu, Jihye Kim, Won Do Heo, Dongseob Tark, Sang-Min Kang

{"title":"Targeting pseudoknots with Cas13b inhibits porcine epidemic diarrhoea virus replication.","authors":"Hee-Jeong Han, Daseuli Yu, Jeonghye Yu, Jihye Kim, Won Do Heo, Dongseob Tark, Sang-Min Kang","doi":"10.1099/jgv.0.002071","DOIUrl":"https://doi.org/10.1099/jgv.0.002071","url":null,"abstract":"Clustered regularly interspaced short palindromic repeats-associated protein 13 (CRISPR-Cas13), an RNA editing technology, has shown potential in combating RNA viruses by degrading viral RNA within mammalian cells. In this study, we demonstrate the effective inhibition of porcine epidemic diarrhoea virus (PEDV) replication and spread using CRISPR-Cas13. We analysed the sequence similarity of the pseudoknot region between PEDV and severe acute respiratory syndrome coronavirus 2, both belonging to the Coronaviridae family, as well as the similarity of the RNA-dependent RNA polymerase (RdRp) gene region among three different strains of the PED virus. Based on this analysis, we synthesized three CRISPR RNAs (crRNAs) targeting the pseudoknot region and the nonpseudoknot region, each for comparison. In cells treated with crRNA #3 targeting the pseudoknot region, RdRp gene expression decreased by 95%, membrane (M) gene expression by 89% and infectious PEDV titre within the cells reduced by over 95%. Additionally, PED viral nucleocapsid (N) and M protein expression levels decreased by 83 and 98%, respectively. The optimal concentration for high antiviral efficacy without cytotoxicity was determined. Treating cells with 1.5 µg of Cas13b mRNA and 0.5 µg of crRNA resulted in no cytotoxicity while achieving over 95% inhibition of PEDV replication. The Cas13b mRNA therapeutics approach was validated as significantly more effective through a comparative study with merafloxacin, a drug targeting the pseudoknot region of the viral genome. Our results indicate that the pseudoknot region plays a crucial role in the degradation of the PEDV genome through the CRISPR-Cas13 system. Therefore, targeting Cas13b to the pseudoknot offers a promising new approach for treating coronavirus infections.","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Erratum: Out-of-sync evolutionary patterns and mutual interplay of major and minor capsid proteins in norovirus GII.2.

IF 3.6 4区医学

Journal of General Virology Pub Date : 2025-02-01 DOI: 10.1099/jgv.0.002074

Ruiquan Xu, Liang Xue, Jingmin Wang, Yiqing Chen, Yingwen Cao, Junshan Gao, Hui Gao, Qingyao Du, Xiaoxia Kou, Lin Yu

引用次数: 0

An improved reverse genetics system for rotavirus vaccine strain LLR using five plasmid vectors. 基于5个质粒载体的轮状病毒疫苗LLR株反向遗传系统的改进。

IF 3.6 4区医学

Journal of General Virology Pub Date : 2025-01-01 DOI: 10.1099/jgv.0.002064

Xiafei Liu, Junjie Yu, Shan Li, Pengdi Chai, Zhiping Xie, Lili Pang, Jinsong Li, Wuyang Zhu, Weihong Ren, Zhaojun Duan

引用次数: 0

Ubiquitin-like modifier-activating enzyme 1 interacts with Zika virus NS5 and promotes viral replication in the infected cell. 泛素样修饰物激活酶1与寨卡病毒NS5相互作用，促进病毒在感染细胞内复制。

IF 3.6 4区医学

Journal of General Virology Pub Date : 2025-01-01 DOI: 10.1099/jgv.0.002063

Imanol Rodrigo, Laura Albentosa-González, María Jos Romero de Ávila, Maria Rosaria Bassi, Raquel Navarro Sempere, Pilar Clemente-Casares, Armando Arias

{"title":"Ubiquitin-like modifier-activating enzyme 1 interacts with Zika virus NS5 and promotes viral replication in the infected cell.","authors":"Imanol Rodrigo, Laura Albentosa-González, María Jos Romero de Ávila, Maria Rosaria Bassi, Raquel Navarro Sempere, Pilar Clemente-Casares, Armando Arias","doi":"10.1099/jgv.0.002063","DOIUrl":"https://doi.org/10.1099/jgv.0.002063","url":null,"abstract":"Translation errors, impaired folding or environmental stressors (e.g. infection) can all lead to an increase in the presence of misfolded proteins. These activate cellular responses to their removal, including intracellular protein degradation activities. Protein ubiquitylation is involved in two major degradation pathways, the ubiquitin-proteasome system and selective autophagy. In humans, the ubiquitin-like modifier-activating enzyme 1 (UBA1) is the primary E1 enzyme in the ubiquitin conjugation cascade. Viruses have evolved to exploit protein degradation pathways to complete their infection cycles. Zika virus (ZIKV) is an emerging orthoflavivirus causing serious neurologic disorders in neonates (congenital microcephaly) and adults (Guillain-Barré syndrome). Non-structural protein 5 (NS5), the largest and most conserved protein in the orthoflaviviruses, catalyses the synthesis and capping of new viral genomes. In addition to viral RNA replication in the cytoplasm, ZIKV NS5 is translocated into the nucleus to interfere with host antiviral responses. Here, we demonstrate that ZIKV NS5 co-immunoprecipitates with cellular UBA1. Immunofluorescence assays suggest that this interaction takes place primarily in the nucleus of an infected cell, although colocalization of both proteins is also detected in the cytosol. RNA interference-mediated depletion of UBA1 leads to reduced virus titres in the infected cells, while transient overexpression of UBA1 favours faster replication kinetics, with higher virus titres and protein levels detected. Moreover, UBA1-targeting drugs cause significant drops in virus infectivity. These results support a proviral role for UBA1 during ZIKV infection and encourage the potential use of inhibitors against this enzyme or its NS5-interacting epitopes as potential therapeutic targets.","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-cycle parainfluenza virus type 5 vectors for producing recombinant proteins, including a humanized anti-V5 tag antibody. 单循环副流感病毒5型载体，用于生产重组蛋白，包括人源化抗v5标签抗体。

IF 3.6 4区医学

Journal of General Virology Pub Date : 2025-01-01 DOI: 10.1099/jgv.0.002061

Richard E Randall, Dan Young, Maria Pisliakova, Jelena Andrejeva, Lynsey West, Luis Rossler, Volker Morath, David Hughes, Steve Goodbourn

引用次数: 0

Linking the function of cis-acting RNA elements to coronavirus replication using interactomes.

IF 3.6 4区医学

Journal of General Virology Pub Date : 2025-01-01 DOI: 10.1099/jgv.0.002070

Yueh-Chun Yao, Chun-Chun Yang, Meilin Wang, Feng-Cheng Hsieh, Ching-Hung Lin, Hsuan-Wei Hsu, Chien-Chen Lai, Wei-Chen Wang, Cheng-Yu Kuo, Cheng-Yao Yang, Hung-Yi Wu

{"title":"Linking the function of cis-acting RNA elements to coronavirus replication using interactomes.","authors":"Yueh-Chun Yao, Chun-Chun Yang, Meilin Wang, Feng-Cheng Hsieh, Ching-Hung Lin, Hsuan-Wei Hsu, Chien-Chen Lai, Wei-Chen Wang, Cheng-Yu Kuo, Cheng-Yao Yang, Hung-Yi Wu","doi":"10.1099/jgv.0.002070","DOIUrl":"https://doi.org/10.1099/jgv.0.002070","url":null,"abstract":"RNA structures that are functionally important are defined as cis-acting RNA elements because their functions cannot be compensated for in trans. The cis-acting RNA elements in the 3' UTR of coronaviruses are important for replication; however, the mechanism linking the cis-acting RNA elements to their replication function remains to be established. In the present study, a comparison of the biological processes of the interactome and the replication efficiency between the 3' UTR cis-acting RNA elements in coronaviruses, including severe acute respiratory syndrome coronavirus 2, suggests that (i) the biological processes, including translation, protein folding and protein stabilization, derived from the analysis of the cis-acting RNA element interactome and (ii) the architecture of the cis-acting RNA elements and their interactomes are highly correlated with coronavirus replication. In addition, alteration of the interactome using the compound 5-benzyloxygramine can cause reduced coronavirus replication, reinforcing the connection between cis-acting RNA elements and replication by interactome. Together, these results link cis-acting RNA elements to the coronavirus replication and establish a model to analyse the cis-acting RNA elements in the replication of RNA viruses by interactome.","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HIV capsids: orchestrators of innate immune evasion, pathogenesis and pandemicity. HIV衣壳：先天免疫逃避、发病机制和流行的策划者。

IF 3.6 4区医学

Journal of General Virology Pub Date : 2025-01-01 DOI: 10.1099/jgv.0.002057

Kate L Morling, Mohamed ElGhazaly, Richard S B Milne, Greg J Towers

{"title":"HIV capsids: orchestrators of innate immune evasion, pathogenesis and pandemicity.","authors":"Kate L Morling, Mohamed ElGhazaly, Richard S B Milne, Greg J Towers","doi":"10.1099/jgv.0.002057","DOIUrl":"https://doi.org/10.1099/jgv.0.002057","url":null,"abstract":"Human immunodeficiency virus (HIV) is an exemplar virus, still the most studied and best understood and a model for mechanisms of viral replication, immune evasion and pathogenesis. In this review, we consider the earliest stages of HIV infection from transport of the virion contents through the cytoplasm to integration of the viral genome into host chromatin. We present a holistic model for the virus-host interaction during this pivotal stage of infection. Central to this process is the HIV capsid. The last 10 years have seen a transformation in the way we understand HIV capsid structure and function. We review key discoveries and present our latest thoughts on the capsid as a dynamic regulator of innate immune evasion and chromatin targeting. We also consider the accessory proteins Vpr and Vpx because they are incorporated into particles where they collaborate with capsids to manipulate defensive cellular responses to infection. We argue that effective regulation of capsid uncoating and evasion of innate immunity define pandemic potential and viral pathogenesis, and we review how comparison of different HIV lineages can reveal what makes pandemic lentiviruses special.","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ICTV Virus Taxonomy Profile: Bromoviridae 2025.

IF 3.6 4区医学

Journal of General Virology Pub Date : 2025-01-01 DOI: 10.1099/jgv.0.002069

Jeremy R Thompson, Tomás Canto, John P Carr, Vicente Pallás, Dana Šafářová

引用次数: 0

A yeast-assembled, plasmid-launched reverse genetics system for the murine coronavirus MHV-A59. 酵母组装，质粒启动小鼠冠状病毒MHV-A59的反向遗传系统。

IF 3.6 4区医学

Journal of General Virology Pub Date : 2025-01-01 DOI: 10.1099/jgv.0.002065

Cade E Sterling, Natalie R Wilson, Debreiona Y Harris, Everett Clinton Smith

{"title":"A yeast-assembled, plasmid-launched reverse genetics system for the murine coronavirus MHV-A59.","authors":"Cade E Sterling, Natalie R Wilson, Debreiona Y Harris, Everett Clinton Smith","doi":"10.1099/jgv.0.002065","DOIUrl":"https://doi.org/10.1099/jgv.0.002065","url":null,"abstract":"The Betacoronavirus murine hepatitis virus (MHV) is an important model system for studying coronavirus (CoV) molecular and cell biology. Despite this, few reagents for MHV are available through repositories such as ATCC or Addgene, potentially limiting the widespread adoption of MHV as a tractable model system. To overcome some challenges inherent in the existing MHV reverse genetics systems, we developed a plasmid-launched transformation-associated recombination (TAR) cloning-based system to assemble the MHV (strain A59; MHV-A59) genome. Following assembly in yeast, virus replication was launched by transfecting the fully assembled genome into HEK-293T cells. MHV-A59 recovered using this TAR cloning-based approach (WTTAR MHV-A59) replicated with kinetics identical to the virus recovered using a ligation- and T7-based approach (WTLIG MHV-A59). Additionally, WTTAR MHV-A59 can be detected at least 10 h post-transfection without requiring additional nucleocapsid (N) provided in trans. Lastly, we demonstrated the tractability of this TAR cloning-based system by recovering MHV-A59 expressing an 11 amino acid-containing HiBiT tag fused to the C-terminus of spike (S). While this virus, SC MHV-A59, replicated with reduced kinetics compared to WTTAR MHV-A59, the kinetics of virion production could be measured over time directly from the supernatant. This report represents the first plasmid-launched, TAR cloning-based system for MHV-A59. Furthermore, it describes a new reporter virus that could be used to study early steps during MHV-A59 entry and be used in the screening of antiviral compounds. To support future research with MHV-A59, we have made the necessary plasmids for this system available through ATCC.","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptional dynamics during Heliothis zea nudivirus 1 infection in an ovarian cell line from Helicoverpa zea. 玉米裸芽病毒1型感染玉米玉米卵巢细胞系的转录动力学。

IF 3.6 4区医学

Journal of General Virology Pub Date : 2025-01-01 DOI: 10.1099/jgv.0.002066

Jirka Manuel Petersen, Astrid Bryon, Annie Bézier, Jean-Michel Drezen, Monique M van Oers

{"title":"Transcriptional dynamics during Heliothis zea nudivirus 1 infection in an ovarian cell line from Helicoverpa zea.","authors":"Jirka Manuel Petersen, Astrid Bryon, Annie Bézier, Jean-Michel Drezen, Monique M van Oers","doi":"10.1099/jgv.0.002066","DOIUrl":"10.1099/jgv.0.002066","url":null,"abstract":"Nudiviruses (family Nudiviridae) are double-stranded DNA viruses that infect various insects and crustaceans. Among them, Heliothis zea nudivirus 1 (HzNV-1) represents the rare case of a lepidopteran nudivirus inducing a sexual pathology. Studies about molecular pathological dynamics of HzNV-1 or other nudiviruses are scarce. Hence, this study aims to provide a transcriptomic profile of HzNV-1 in an ovary-derived cell line of Helicoverpa zea (HZ-AM1), during early (3, 6 and 9 h post-infection) and advanced (12 and 24 h post-infection) stages of infection. Total RNA was extracted from both virus- and mock-infected cells, and RNA-seq analysis was performed to examine both virus and host transcriptional dynamics. Hierarchical clustering was used to categorize viral genes, while differential gene expression analysis was utilized to pinpoint host genes that are significantly affected by the infection. Hierarchical clustering classified the 154 HzNV-1 genes into four temporal phases, with early phases mainly involving transcription and replication genes and later phases including genes for virion assembly. In addition, a novel viral promoter motif was identified in the upstream region of early-expressed genes. Host gene analysis revealed significant upregulation of heat shock protein genes and downregulation of histone genes. The identification of temporal patterns in viral gene expression enhances the molecular understanding of nudivirus pathology, while the identified differentially expressed host genes highlight the key pathways most hijacked by HzNV-1 infection.","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"106 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0