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Intra-host variability of SARS-CoV-2: Patterns, causes and impact on COVID-19. SARS-CoV-2 的宿主内变异：模式、原因和对 COVID-19 的影响。
Virology Pub Date : 2024-12-22 DOI: 10.1016/j.virol.2024.110366
Leandro R Jones
{"title":"Intra-host variability of SARS-CoV-2: Patterns, causes and impact on COVID-19.","authors":"Leandro R Jones","doi":"10.1016/j.virol.2024.110366","DOIUrl":"https://doi.org/10.1016/j.virol.2024.110366","url":null,"abstract":"<p><p>Intra-host viral variability is related to pathogenicity, persistence, drug resistance, and the emergence of new clades. This work reviews the large amount of data on SARS-CoV-2 intra-host variability accumulated to date, addressing known and potential implications in COVID-19 and the emergence of VOCs and lineage-defining mutations. Topics covered include the distribution of intra-host polymorphisms across the genome, the corresponding mutational signatures, their patterns of emergence and extinction throughout infection, and the processes governing their abundance, frequency, and type (synonymous, nonsynonymous, indels, nonsense). Besides, evidence is reviewed that the virus can replicate and mutate in isolation at different anatomical compartments, which may imply that what we have learned from respiratory samples could be part of a broader picture.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"603 ","pages":"110366"},"PeriodicalIF":0.0,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Imaging of viral replication in live cells by using split fluorescent protein-tagged reporter flaviviruses. 利用分裂荧光蛋白标记的报告病毒黄病毒在活细胞中的复制成像。
Virology Pub Date : 2024-12-22 DOI: 10.1016/j.virol.2024.110374
Ping Yang, Zheng-Jian Wang, Hai-Tao Lu, Xu-Meng Feng, Jing-Long Ye, Guangchuan Wang, Cheng-Feng Qin, Qing Ye, Zhong-Yu Liu
{"title":"Imaging of viral replication in live cells by using split fluorescent protein-tagged reporter flaviviruses.","authors":"Ping Yang, Zheng-Jian Wang, Hai-Tao Lu, Xu-Meng Feng, Jing-Long Ye, Guangchuan Wang, Cheng-Feng Qin, Qing Ye, Zhong-Yu Liu","doi":"10.1016/j.virol.2024.110374","DOIUrl":"https://doi.org/10.1016/j.virol.2024.110374","url":null,"abstract":"<p><p>The knowledge on the life cycle of flaviviruses is still incomplete, and no direct-acting antivirals against their infections are clinically available. Herein, by screening via a Zika virus (ZIKV) replicon assay, we found that the N-terminus of NS2A exhibited great tolerance to the insertions of different split fluorescent proteins (split-FPs). Furthermore, both ZIKV and dengue virus encoding a split-FP-tagged NS2A propagated efficiently, and the split-FP-tagged ZIKVs had good genetic stability. Robust green fluorescence was observed in the reporter cell lines infected with these viruses and the fluorescence responded to anti-flavivirus chemicals with high specificity and sensitivity. Moreover, the sites of viral RNA replication were illuminated in live cells. Interestingly, by blocking viral RNA synthesis with an NS5 inhibitor, we found a correlation between the morphological characteristics of potential replication organelles and RNA amplification, highlighting that the NS2A-tagged viruses are of great value for the in-depth understanding of flavivirus replication mechanisms.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"603 ","pages":"110374"},"PeriodicalIF":0.0,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multiple sphingolipid-metabolizing enzymes modulate influenza virus replication. 多种鞘脂代谢酶调节流感病毒的复制。
Virology Pub Date : 2024-12-22 DOI: 10.1016/j.virol.2024.110367
Savannah McKenna, Kwang Il Jung, Jennifer J Wolf, Young-Jin Seo, Bumsuk Hahm
{"title":"Multiple sphingolipid-metabolizing enzymes modulate influenza virus replication.","authors":"Savannah McKenna, Kwang Il Jung, Jennifer J Wolf, Young-Jin Seo, Bumsuk Hahm","doi":"10.1016/j.virol.2024.110367","DOIUrl":"https://doi.org/10.1016/j.virol.2024.110367","url":null,"abstract":"<p><p>The sphingolipid network is sustained principally by the balance of bioactive sphingolipid molecules and their regulation by sphingolipid-metabolizing enzymes. The components in the lipid system display key functions in numerous cellular and disease conditions including virus infections. During the COVID-19 pandemic, there was a fruitful effort to use an inhibitor that blocks the activity of sphingosine kinase (SphK) 2 to cure the devastating disease. Support for the inhibitor came from pre-clinical research on influenza where the inhibitor demonstrated effective protection of mice from influenza-induced morbidity and mortality. This highlights the importance of basic and translational research on the sphingolipid system for improving human health. Multiple sphingolipid-metabolizing enzymes have been reported to regulate influenza virus replication and propagation. In this review, the emphasis is placed on the roles of these enzymes that impact influenza virus life cycle and the conceivable mechanisms for the interplay between influenza virus and the sphingolipid pathway.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"603 ","pages":"110367"},"PeriodicalIF":0.0,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
LEF3 phosphorylation attenuates the replication of Bombyx mori nucleopolyhedrovirus by suppressing its interaction with alkaline nuclease. LEF3磷酸化通过抑制家蚕核多角体病毒与碱性核酸酶的相互作用而减弱其复制。
Virology Pub Date : 2024-12-21 DOI: 10.1016/j.virol.2024.110369
Chaoguang Gu, Yuqian Mo, Jiaqi Li, Xizhen Zhang, Siqi Xu, Meng Miao, Yanping Quan, Wei Yu
{"title":"LEF3 phosphorylation attenuates the replication of Bombyx mori nucleopolyhedrovirus by suppressing its interaction with alkaline nuclease.","authors":"Chaoguang Gu, Yuqian Mo, Jiaqi Li, Xizhen Zhang, Siqi Xu, Meng Miao, Yanping Quan, Wei Yu","doi":"10.1016/j.virol.2024.110369","DOIUrl":"https://doi.org/10.1016/j.virol.2024.110369","url":null,"abstract":"<p><p>Late expression factor 3 (LEF3), a multifunctional single-stranded DNA binding protein encoded by baculoviruses, is indispensable for viral DNA replication and plays a pivotal role in viral infection. Our previous quantitative analysis of phosphorylomics revealed that the phosphorylation levels of two serine residues (S8 and S25) located in LEF3 nuclear localization sequence were significantly up-regulated after Bombyx mori nucleopolyhedrovirus (BmNPV) infection, but the underlying mechanism remained unknown. To investigate the impact of phosphorylation on BmNPV infection, site-direct mutagenesis was performed on LEF3 to obtain phosphorylated mimic (S/D) or dephosphorylated mimic (S/A) mutants. The results demonstrated that the viral replication and proliferation were inhibited by phosphorylation of S8 or S25. Furthermore, we found that the N-terminal 125 amino acids region was responsible for interacting with virus-encoded alkaline nuclease, but this interaction could be suppressed by the phosphorylation. Our findings indicated that phosphorylation may serve as an antiviral strategy for host.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"603 ","pages":"110369"},"PeriodicalIF":0.0,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Host microRNAs as regulators of porcine reproductive and respiratory syndrome virus infection. 作为猪繁殖与呼吸综合征病毒感染调节因子的宿主微RNA。
Virology Pub Date : 2024-12-21 DOI: 10.1016/j.virol.2024.110361
Shu-Yuan Guo, Wen-Hai Feng
{"title":"Host microRNAs as regulators of porcine reproductive and respiratory syndrome virus infection.","authors":"Shu-Yuan Guo, Wen-Hai Feng","doi":"10.1016/j.virol.2024.110361","DOIUrl":"https://doi.org/10.1016/j.virol.2024.110361","url":null,"abstract":"<p><p>Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a significant pathogen in the swine industry. MicroRNAs (miRNAs), a class of small non-coding RNA molecules, have risen to prominence as key regulators of gene expression at the post-transcriptional level. Their significance in regulating virus-host interactions is now widely acknowledged. So far, more than 30 miRNAs have been found to play a role in PRRSV infection. They can regulate viral genome stability and protein synthesis by targeting PRRSV RNA, and modulate the host immune response, thus affecting PRRSV replication. Understanding the role of miRNAs in PRRSV infection can further elucidate the pathogenesis of PRRSV and pave the way for the development of new antiviral strategies through miRNA-based therapies. This review will focus on how host miRNAs alter PRRSV infection, underscoring their multifaceted involvement in the interplay between virus and host.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"603 ","pages":"110361"},"PeriodicalIF":0.0,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cellular takeover: How new world alphaviruses impact host organelle function. 细胞接管：新的世界甲病毒如何影响宿主细胞器功能。
Virology Pub Date : 2024-12-20 DOI: 10.1016/j.virol.2024.110365
Morgen VanderGiessen, Abdullahi Jamiu, Brittany Heath, Ivan Akhrymuk, Kylene Kehn-Hall
{"title":"Cellular takeover: How new world alphaviruses impact host organelle function.","authors":"Morgen VanderGiessen, Abdullahi Jamiu, Brittany Heath, Ivan Akhrymuk, Kylene Kehn-Hall","doi":"10.1016/j.virol.2024.110365","DOIUrl":"https://doi.org/10.1016/j.virol.2024.110365","url":null,"abstract":"<p><p>Alphavirus replication is dependent on host cell organelles to facilitate multiple steps of the viral life cycle. New world alphaviruses (NWA) consisting of eastern, western and Venezuelan equine encephalitis viruses are a subgroup of alphaviruses associated with central nervous system disease. Despite differing morbidity and mortality amongst these viruses, all are important human pathogens due to their transmission through viral aerosolization and mosquito transmission. In this review, we summarize the utilization of host organelles for NWA replication and the subversion of the host innate immune responses. The impact of viral proteins and replication processes on organelle function is also discussed. Literature involving old world alphaviruses (OWA), such as chikungunya virus and Sindbis virus, is included to compare and contrast between OWA and NWA and highlight gaps in knowledge for NWA. Finally, potential targets for therapeutics or vaccine candidates are highlighted with a focus on host-directed therapeutics.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"603 ","pages":"110365"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Eliminating the persistent HIV reservoir based on biomarker expression - How do we get there? 基于生物标志物表达消除持久性HIV病毒库-我们如何实现这一目标？
Virology Pub Date : 2024-12-19 DOI: 10.1016/j.virol.2024.110368
Nadejda Beliakova-Bethell
{"title":"Eliminating the persistent HIV reservoir based on biomarker expression - How do we get there?","authors":"Nadejda Beliakova-Bethell","doi":"10.1016/j.virol.2024.110368","DOIUrl":"https://doi.org/10.1016/j.virol.2024.110368","url":null,"abstract":"<p><p>Persistent HIV reservoir with different levels of proviral transcriptional activity represents a hurdle to HIV cure. The absence of a specific molecular signature or a \"biomarker\" to define cells latently infected with HIV limits reservoir eradication efforts. Biomarkers proposed in the literature define subsets of latently infected cells. This article discusses factors contributing to biomarker heterogeneity: external stimuli the cells are exposed to, tissue microenvironments, and person-to-person variation. Despite reservoir heterogeneity, several biomarkers, e.g., programmed cell death 1 and the Fc fragment of IgG low affinity IIa receptor, were reported consistently in multiple studies; however, they alone are unlikely to define all the HIV reservoir cells. Identifying a minimal set of cell surface proteins that together define all reservoir subsets is needed. Future studies will need to focus on the identification of co-expressed proteins that define the same sets of cells to reduce the number of proteins in a biomarker panel. A detailed characterization of tissue biomarkers and proteins expressed in latently infected cells of the myeloid lineage is needed to ensure that all the reservoirs are targeted throughout the body. Furthermore, the effect of underlying conditions that develop as people with HIV age on the manifestation of latency should be evaluated. With the development of novel technologies, such as spatial transcriptomics and proteomics, such endeavors will soon be possible. Thus, there is promise that a minimal set of proteins defining all the different reservoir subsets can be identified and developed into a reservoir targeting strategy.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"603 ","pages":"110368"},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel exploitation of autophagy by tombusviruses. 瘤状病毒自噬的新开发。
Virology Pub Date : 2024-12-17 DOI: 10.1016/j.virol.2024.110363
Peter D Nagy, Judit Pogany, Yuanrong Kang
{"title":"Novel exploitation of autophagy by tombusviruses.","authors":"Peter D Nagy, Judit Pogany, Yuanrong Kang","doi":"10.1016/j.virol.2024.110363","DOIUrl":"https://doi.org/10.1016/j.virol.2024.110363","url":null,"abstract":"<p><p>Positive-strand (+)RNA viruses are major pathogens of humans, animals and plants. This review summarizes the complex interplay between the host autophagy pathway and Tomato bushy stunt virus (TBSV) replication. Recent discoveries with TBSV have revealed virus-driven exploitation of autophagy in multiple ways that contributes to the unique phospholipid composition of viral replication organellar (VROs) membranes. Viral replication protein-driven subversion of phagophore membranes, recruitment of ATG2 bulk lipid transfer protein to enrich phosphatidylethanolamine and phosphatidylserine in VROs, recruitment of VPS34 PI3K to produce PI(3)P; and ATG11-facilitated formation of stable viral membrane contact sites contributes to VRO membrane proliferation. Recruitment of autophagy core proteins to vir-NBR1 bodies within vir-condensates associated with VROs results in dampened antiviral degradation by autophagy. Overall, TBSV intricate interplay with the autophagy machinery highlights the importance of lipid dynamics in viral life cycles and points toward potential directions for therapeutic intervention.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"603 ","pages":"110363"},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
30 years of HIV therapy: Current and future antiviral drug targets. 30年的HIV治疗：当前和未来的抗病毒药物靶点。
Virology Pub Date : 2024-12-17 DOI: 10.1016/j.virol.2024.110362
Julius Nuwagaba, Jessica A Li, Brandon Ngo, Richard E Sutton
{"title":"30 years of HIV therapy: Current and future antiviral drug targets.","authors":"Julius Nuwagaba, Jessica A Li, Brandon Ngo, Richard E Sutton","doi":"10.1016/j.virol.2024.110362","DOIUrl":"https://doi.org/10.1016/j.virol.2024.110362","url":null,"abstract":"<p><p>Significant advances in treatment have turned HIV-1 into a manageable chronic condition. This has been achieved due to highly active antiretroviral therapy (HAART), involving a combination regimen of medications, including drugs that target Reverse Transcriptase, Protease, Integrase, and viral entry, explored in this review. This paper also highlights novel therapies, such as Lenacapavir, and avenues toward functional cure targeting the CCR5 co-receptor, including the Δ32 mutation. Challenges of HAART include lifelong adherence, toxicity, drug interactions, and drug resistance. Future therapeutic strategies may focus on underexplored antiviral targets. HIV-1 Tat and Rev proteins have essential HIV-1 regulatory functions of transcriptional elongation of the viral long terminal repeat and nuclear export of intron-containing HIV-1 RNA, respectively. These non-enzymatic proteins should thus be investigated to identify small molecules that inhibit HIV-1 replication, without causing undue toxicity. Continued innovation is essential to address therapeutic gaps and bring us closer to a potential HIV-1 cure.</p>","PeriodicalId":94266,"journal":{"name":"Virology","volume":"603 ","pages":"110362"},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to "Developing adenoviral vectors encoding therapeutic genes toxic to host cells: Comparing binary and single-inducible vectors expressing truncated E2F-1" [Virology 397 (2010) 337-345]. “开发对宿主细胞有毒的治疗性基因的腺病毒载体：比较表达截断的E2F-1的双诱导和单诱导载体”的更正[病毒学397(2010)337-345]。
Virology Pub Date : 2024-12-16 DOI: 10.1016/j.virol.2024.110355
Jorge G Gomez-Gutierrez, Xia-Mei Rao, Aracely Garcia-Garcia, Hongying Hao, Kelly M McMasters, H Sam Zhou
{"title":"Corrigendum to \"Developing adenoviral vectors encoding therapeutic genes toxic to host cells: Comparing binary and single-inducible vectors expressing truncated E2F-1\" [Virology 397 (2010) 337-345].","authors":"Jorge G Gomez-Gutierrez, Xia-Mei Rao, Aracely Garcia-Garcia, Hongying Hao, Kelly M McMasters, H Sam Zhou","doi":"10.1016/j.virol.2024.110355","DOIUrl":"https://doi.org/10.1016/j.virol.2024.110355","url":null,"abstract":"","PeriodicalId":94266,"journal":{"name":"Virology","volume":" ","pages":"110355"},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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