Virus research最新文献

{"title":"Epidemic characteristics of local HIV-2 transmission across Hunan province, China","authors":"Xiaobai Zou ,&nbsp;Jianmei He ,&nbsp;Xiaojun Li ,&nbsp;Jun Zheng ,&nbsp;Xiaolin Su ,&nbsp;Jie Chen ,&nbsp;Xi Chen","doi":"10.1016/j.virusres.2024.199385","DOIUrl":"10.1016/j.virusres.2024.199385","url":null,"abstract":"<div><h3>Objective</h3><p>To elucidate the epidemiological features of HIV-2 in Hunan Province, China, utilizing sequence analysis.</p></div><div><h3>Methods</h3><p>Thirteen individuals diagnosed with HIV-2 infection in Hunan Province, China, from 2017 to 2023 were included in this study. Amplification of HIV-2 <em>env</em> and <em>pol</em> regions was conducted, followed by Sanger sequencing. Phylogenetic and molecular transmission network analyses were performed to delineate molecular features and transmission dynamics.</p></div><div><h3>Results</h3><p>All 14 individuals contracted HIV-2 through heterosexual intercourse, comprising 7 males and 7 females, with a median age of 58 years. Among them, three couples (HN001 and HN013, HN010 and HN011, HN008 and HN009) were identified, along with commercial sexual activity engagement reported for subject HN004. Notably, subjects HN001, HN003, HN008, and HN010 engaged in commercial sexual activities at the same location as subject HN004. Phylogenetic analysis of the <em>pol</em> gene revealed close proximity of sequences from all subjects to reference sequences from Gambia (Sub-type A). Employing a genetic distance threshold of 1.5 %, eight out of the 14 subjects formed a molecular transmission network, with HN002 and HN004 identified as central nodes.</p></div><div><h3>Conclusion</h3><p>From 2017 to 2023, all HIV-2-infected individuals in Hunan Province, China, acquired the virus through identifiable routes, indicating transmission of similar HIV-2 strains among them.</p></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168170224000789/pdfft?md5=e6517ab85d63792e3d426b6ae4ef97ac&pid=1-s2.0-S0168170224000789-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899738","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}

{"title":"Exploration of influenza A virus PA protein-associated cellular proteins discloses its impact on mitochondrial function","authors":"Chih-Ching Wu ,&nbsp;Ee-Hong Tam ,&nbsp;Yu-Yin Shih ,&nbsp;Yi-Ru Lin ,&nbsp;Pei-Chun Hsueh ,&nbsp;Hsiang-Yi Shen ,&nbsp;Chian-Huey Woung ,&nbsp;Li-Ting Wang ,&nbsp;Jia-Chen Tsai ,&nbsp;Syh-Jae Lin ,&nbsp;Chuang-Rung Chang ,&nbsp;Po-Yuan Ke ,&nbsp;Rei-Lin Kuo","doi":"10.1016/j.virusres.2024.199387","DOIUrl":"10.1016/j.virusres.2024.199387","url":null,"abstract":"<div><p>Influenza A virus can infect respiratory tracts and may cause severe illness in humans. Proteins encoded by influenza A virus can interact with cellular factors and dysregulate host biological processes to support viral replication and cause pathogenicity. The influenza viral PA protein is not only a subunit of influenza viral polymerase but also a virulence factor involved in pathogenicity during infection. To explore the role of the influenza virus PA protein in regulating host biological processes, we performed immunoprecipitation and LC‒MS/MS to globally identify cellular factors that interact with the PA proteins of the influenza A H1N1, 2009 pandemic H1N1, and H3N2 viruses. The results demonstrated that proteins located in the mitochondrion, proteasome, and nucleus are associated with the PA protein. We further discovered that the PA protein is partly located in mitochondria by immunofluorescence and mitochondrial fractionation and that overexpression of the PA protein reduces mitochondrial respiration. In addition, our results revealed the interaction between PA and the mitochondrial matrix protein PYCR2 and the antiviral role of PYCR2 during influenza A virus replication. Moreover, we found that the PA protein could also trigger autophagy and disrupt mitochondrial homeostasis. Overall, our research revealed the impacts of the influenza A virus PA protein on mitochondrial function and autophagy.</p></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168170224000807/pdfft?md5=43c51c1cf2239e01506996ff71975ec4&pid=1-s2.0-S0168170224000807-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890618","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}

{"title":"Genome comparison of long-circulating field CnmeGV isolates from the same region","authors":"Yachao Zuo,&nbsp;Jiawen Yang,&nbsp;Hao Zhang,&nbsp;Lu Li,&nbsp;Jing Luo,&nbsp;Yanrong Lv,&nbsp;Meijin Yuan,&nbsp;Kai Yang","doi":"10.1016/j.virusres.2024.199390","DOIUrl":"10.1016/j.virusres.2024.199390","url":null,"abstract":"<div><p>Cnaphalocrocis medinalis granulovirus (CnmeGV), belonging to <em>Betabaculovirus cnamedinalis</em>, can infect the rice pest, the rice leaf roller. In 1979, a CnmeGV isolate, CnmeGV-EP, was collected from Enping County, China. In 2014, we collected another CnmeGV isolate, CnmeGV-EPDH3, at the same location and obtained the complete virus genome sequence using Illumina and ONT sequencing technologies. By combining these two virus isolates, we updated the genome annotation of CnmeGV and conducted an in-depth analysis of its genome features. CnmeGV genome contains abundant tandem repeat sequences, and the repeating units in the homologous regions (<em>hrs</em>) exhibit overlapping and nested patterns. The genetic variations within EPDH3 population show the high stability of CnmeGV genome, and tandem repeats are the only region of high genetic variation in CnmeGV genome replication. Some defective viral genomes formed by recombination were found within the population. Comparison analysis of the two virus isolates collected from Enping showed that the proteins encoded by the CnmeGV-specific genes were less conserved relative to the baculovirus core genes. At the genomic level, there are a large number of SNPs and InDels between the two virus isolates, especially in and around the <em>bro</em> genes and <em>hrs</em>. Additionally, we discovered that CnmeGV acquired a segment of non-ORF sequence from its host, which does not provide any new proteins but rather serves as redundant genetic material integrated into the viral genome. Furthermore, we observed that the host's transposon piggyBac has inserted into some virus genes. Together, dsDNA viruses could acquire non-coding genetic material from their hosts to expand the size of their genomes. These findings provide new insights into the evolution of dsDNA viruses.</p></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168170224000832/pdfft?md5=f684afdc636416d9f875e162a8574c9c&pid=1-s2.0-S0168170224000832-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868253","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}

{"title":"Exploring the viral landscape of saffron through metatranscriptomic analysis","authors":"Cristian Martínez-Fajardo ,&nbsp;Pablo Navarro-Simarro ,&nbsp;Lucía Morote ,&nbsp;Ángela Rubio-Moraga ,&nbsp;María Mondéjar-López ,&nbsp;Enrique Niza ,&nbsp;Javier Argandoña ,&nbsp;Oussama Ahrazem ,&nbsp;Lourdes Gómez-Gómez ,&nbsp;Alberto José López-Jiménez","doi":"10.1016/j.virusres.2024.199389","DOIUrl":"10.1016/j.virusres.2024.199389","url":null,"abstract":"<div><p>Saffron (<em>Crocus sativus</em> L.), a historically significant crop valued for its nutraceutical properties, has been poorly explored from a phytosanitary perspective. This study conducted a thorough examination of viruses affecting saffron samples from Spanish cultivars, using high-throughput sequencing alongside a systematic survey of transcriptomic datasets from <em>Crocus sativus</em> at the Sequence Read Archive. Our analysis unveiled a broad diversity and abundance, identifying 17 viruses across the 52 analyzed libraries, some of which were highly prevalent. This includes known saffron-infecting viruses and previously unreported ones. In addition, we discovered 7 novel viruses from the <em>Alphaflexiviridae, Betaflexiviridae, Potyviridae, Solemoviridae</em>, and <em>Geminiviridae</em> families, with some present in libraries from various locations. These findings indicate that the saffron-associated virome is more complex than previously reported, emphasizing the potential of phytosanitary analysis to enhance saffron productivity.</p></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168170224000820/pdfft?md5=c7c5091ac834dc6b49a402144cc7b7e3&pid=1-s2.0-S0168170224000820-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140877457","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}

{"title":"The alteration of NK cells phenotypes related to the functions and dengue disease outcomes","authors":"Napas Taechasan ,&nbsp;Iris Scherwitzl ,&nbsp;Piyada Supasa ,&nbsp;Wanwisa Dejnirattisai ,&nbsp;Kanokwan Sriruksa ,&nbsp;Wannee Limpitikul ,&nbsp;Prida Malasit ,&nbsp;Gavin R Screaton ,&nbsp;Juthathip Mongkolsapaya ,&nbsp;Thaneeya Duangchinda","doi":"10.1016/j.virusres.2024.199382","DOIUrl":"10.1016/j.virusres.2024.199382","url":null,"abstract":"<div><p>Natural killer cells (NK cells) are the front line of immune cells to combat pathogens and able to influence the subsequent adaptive immune responses. One of the factors contributing to pathogenesis in dengue hemorrhagic fever (DHF) disease is aberrant immune activation during early phase of infection. This study explored the profile of NK cells in dengue infected pediatric patients with different degrees of disease severity. DHF patients contained higher frequency of activated NK cells but lower ratio of CD56^dim:CD56^bright NK subsets. Activated NK cells exhibited alterations in several NK receptors. Interestingly, the frequencies of NKp30 expressing activated NK cells were more pronounced in dengue fever (DF) than in DHF pediatric patients. <em>In vitro</em> functional analysis indicated that degranulation of NK cells in responding to dengue infected dendritic cells (DCs) required cell-cell contact and type I IFNs. Meanwhile, Interferon gamma (IFN-γ) production initially required cell-cell contact and type I IFNs followed by Interleukin-12 (IL-12), Interleukin-15 (IL-15) and Interleukin-18 (IL-18) resulting in the amplification of IFN-γ producing NK cells over time. This study highlighted the complexity and the factors influencing NK cells responses to dengue virus. Degree of activation, phenotypes of activated cells and the crosstalk between NK cells and other immune cells, could modulate the outcome of NK cells function in the dengue disease.</p></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168170224000753/pdfft?md5=33cb84c448240947c962cc966a9032d5&pid=1-s2.0-S0168170224000753-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869036","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}

{"title":"Impact of Annexin A2 on virus life cycles","authors":"In-Woo Park,&nbsp;Hope K. Fiadjoe,&nbsp;Pankaj Chaudhary","doi":"10.1016/j.virusres.2024.199384","DOIUrl":"10.1016/j.virusres.2024.199384","url":null,"abstract":"<div><p>Due to the limited size of viral genomes, hijacking host machinery by the viruses taking place throughout the virus life cycle is inevitable for the survival and proliferation of the virus in the infected hosts. Recent reports indicated that Annexin A2 (AnxA2), a calcium- and lipid-binding cellular protein, plays an important role as a critical regulator in various steps of the virus life cycle. The multifarious AnxA2 functions in cells, such as adhesion, adsorption, endocytosis, exocytosis, cell proliferation and division, inflammation, cancer metastasis, angiogenesis, etc., are intimately related to the various clinical courses of viral infection. Ubiquitous expression of AnxA2 across multiple cell types indicates the broad range of susceptibility of diverse species of the virus to induce disparate viral disease in various tissues, and intracellular expression of AnxA2 in the cytoplasmic membrane, cytosol, and nucleus suggests the involvement of AnxA2 in the regulation of the different stages of various virus life cycles within host cells. However, it is yet unclear as to the molecular processes on how AnxA2 and the infected virus interplay to regulate virus life cycles and thereby the virus-associated disease courses, and hence elucidation of the molecular mechanisms on AnxA2-mediated virus life cycle will provide essential clues to develop therapeutics deterring viral disease.</p></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168170224000777/pdfft?md5=86e53a9843bda26eb39384f95485221c&pid=1-s2.0-S0168170224000777-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859059","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}

{"title":"NLRP3-dependent pyroptosis exacerbates coxsackievirus A16 and coxsackievirus A10-induced inflammatory response and viral replication in SH-SY5Y cells","authors":"Yajie Hu ,&nbsp;Wei Zhao ,&nbsp;Yaming Lv ,&nbsp;Hui Li ,&nbsp;Jiang Li ,&nbsp;Mingmei Zhong ,&nbsp;Dandan Pu ,&nbsp;Fuping Jian ,&nbsp;Jie Song ,&nbsp;Yunhui Zhang","doi":"10.1016/j.virusres.2024.199386","DOIUrl":"10.1016/j.virusres.2024.199386","url":null,"abstract":"<div><p>Coxsackievirus A16 (CV-A16) and coxsackievirus A10 (CV-A10), more commonly etiological agents of hand, foot and mouth disease (HFMD), are capable of causing severe neurological syndromes with high fatalities, but their neuropathogenesis has rarely been studied. Mounting evidence indicated that pyroptosis is an inflammatory form of cell death that might be widely involved in the pathogenic mechanisms of neurotropic viruses. Our study was designed to examine the effects of NLRP3-mediated pyroptosis in CV-A16- and CV-A10-induced inflammatory neuropathologic formation. In this work, it was showed that SH-SY5Y cells were susceptible to CV-A16 and CV-A10, and meanwhile their infections could result in a decreasing cell viability and an increasing LDH release as well as Caspase1 activation. Moreover, CV-A16 and CV-A10 infections triggered NLRP3-mediated pyroptosis and promoted the release of inflammatory cytokines. Additionally, activated NLRP3 accelerated the pyroptosis formation and aggravated the inflammatory response, but inhibited NLRP3 had a dampening effect on the above situation. Finally, it was further revealed that NLRP3 agonist enhanced the viral replication, but NLRP3 inhibitor suppressed the viral replication, suggesting that NLRP3-driven pyroptosis might support CV-A16 and CV-A10 production in SH-SY5Y cells. Together, our findings demonstrated a mechanism by which CV-A16 and CV-A10 induce inflammatory responses by evoking NLRP3 inflammasome-regulated pyroptosis, which in turn further stimulated the viral replication, providing novel insights into the pathogenesis of CV-A16 and CV-A10 infections.</p></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168170224000790/pdfft?md5=d8f86b151ff9cde8f67c0aecd8b55d8b&pid=1-s2.0-S0168170224000790-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140866541","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}

{"title":"A dual-targeting approach using a human bispecific antibody against the receptor-binding domain of the Middle East Respiratory Syndrome Coronavirus","authors":"Ji Hyun Lee ,&nbsp;Ji Woong Kim ,&nbsp;Hee Eon Lee ,&nbsp;Jin Young Song ,&nbsp;Ah Hyun Cho ,&nbsp;Jae Hyeon Hwang ,&nbsp;Kyun Heo ,&nbsp;Sukmook Lee","doi":"10.1016/j.virusres.2024.199383","DOIUrl":"https://doi.org/10.1016/j.virusres.2024.199383","url":null,"abstract":"<div><p>The emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has posed a significant global health concern due to its severe respiratory illness and high fatality rate. Currently, despite the potential for resurgence, there are no specific treatments for MERS-CoV, and only supportive care is available. Our study aimed to address this therapeutic gap by developing a potent neutralizing bispecific antibody (bsAb) against MERS-CoV. Initially, we isolated four human monoclonal antibodies (mAbs) that specifically target the MERS-CoV receptor-binding domain (RBD) using phage display technology and an established human antibody library. Among these four selected mAbs, our intensive <em>in vitro</em> functional analyses showed that the MERS-CoV RBD-specific mAb K111.3 exhibited the most potent neutralizing activity against MERS-CoV pseudoviral infection and the molecular interaction between MERS-CoV RBD and human dipeptidyl peptidase 4. Consequently, we engineered a novel bsAb, K207.C, by utilizing K111.3 as the IgG base and fusing it with the single-chain variable fragment of its non-competing pair, K111.1. This engineered bsAb showed significantly enhanced neutralization potential against MERS-CoV compared to its parental mAb. These findings suggest that K207.C may serve as a potential candidate for effective MERS-CoV neutralization, further highlighting the promise of the bsAb dual-targeting approach in MERS-CoV neutralization.</p></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168170224000765/pdfft?md5=3ccba8a2a6a3d3d09eb116ac22acad03&pid=1-s2.0-S0168170224000765-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140823372","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}

{"title":"The glycosylation sites in RBD of spike protein attenuate the immunogenicity of PEDV AH2012/12","authors":"Gege Zhang ,&nbsp;Qi Peng ,&nbsp;Shiyu Liu ,&nbsp;Baochao Fan ,&nbsp;Chuanhong Wang ,&nbsp;Xu Song ,&nbsp;Qiuxia Cao ,&nbsp;Chengcheng Li ,&nbsp;Hong Xu ,&nbsp;Hongting Lu ,&nbsp;Meiying Bao ,&nbsp;Shanshan Yang ,&nbsp;Yunchuan Li ,&nbsp;Jiaxiang Wang ,&nbsp;Bin Li","doi":"10.1016/j.virusres.2024.199381","DOIUrl":"https://doi.org/10.1016/j.virusres.2024.199381","url":null,"abstract":"<div><p>Porcine epidemic diarrhea (PED) is a highly contagious swine intestinal disease caused by PED virus (PEDV). Vaccination is a promising strategy to prevent and control PED. Previous studies have confirmed that glycosylation could regulate the immunogenicity of viral antigens. In this study, we constructed three recombinant PEDVs which removed the glycosylation sites in RBD. Viral infection assays revealed that similar replication characteristics between the recombinant viruses and parental PEDV. Although animal challenging study demonstrated that the glycosylation sites in RBD do not affect the pathogenicity of PEDV, we found that removing the glycosylation sites on the RBD regions could promote the IgG and neutralization titer <em>in vivo</em>, suggesting deglycosylation in RBD could enhance the immunogenicity of PEDV. These findings demonstrated that removal of the glycosylation sites in RBD is a promising method to develop PEDV vaccines.</p></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168170224000741/pdfft?md5=3bd0414b966b07c43e55793e98da314a&pid=1-s2.0-S0168170224000741-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140823371","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}

{"title":"Amino acid substitution of the membrane-proximal external region alter neutralization sensitivity in a chronic HIV-1 clade B infected patient","authors":"Yuyu Fu ,&nbsp;Shuhui Wang ,&nbsp;Yanling Hao ,&nbsp;Dan Li ,&nbsp;Li Ren ,&nbsp;Zheng Wang ,&nbsp;Ran Chen ,&nbsp;Wenqi Tang ,&nbsp;Xiuli Shen ,&nbsp;Wanqi Ni ,&nbsp;Yutao Shi ,&nbsp;Meiling Zhu ,&nbsp;Yiming Shao ,&nbsp;Ying Liu","doi":"10.1016/j.virusres.2024.199377","DOIUrl":"10.1016/j.virusres.2024.199377","url":null,"abstract":"<div><p>The membrane-proximal external region (MPER) represents a highly conserved region of the Human Immunodeficiency Virus (HIV) envelope glycoprotein (<em>env</em>) targeted by several broadly neutralizing antibodies (bnAbs). In this study, we employed single genome amplification to amplify 34 full-length <em>env</em> sequences from the 2005 plasma sample of CBJC504, a chronic HIV-1 clade B infected individual. We identified three amino acid changes (N671S, D674N, and K677R) in the MPER. A longitudinal analysis revealed that the proportion of <em>env</em> sequences with MPER mutations increased from 26.5 % in 2005 to 56.0 % in 2009, and the sequences with the same mutation clustered together. Nine functional pseudoviruses were generated from the 34 <em>env</em> sequences to examine the effect of these mutations on neutralizing activity. Pseudoviruses carrying N674 or R677 mutations demonstrate increased sensitivity to autologous plasma and monoclonal antibodies 2F5, 4E10, and 10E8. Reverse mutations were performed in <em>env</em> including N674, R677, D659, and S671/N677 mutations, to validate the impact of the mutations on neutralizing sensitivity. Neutralization assays indicated that the N671S mutation increased neutralization sensitivity to 2F5 and 10E8. The amino acid R at position 677 increased viral resistance to 10E8, whereas N enhanced viral resistance to 4E10 and 10E8. It has been proposed that critical amino acids in the extra-MPER and the number of potential N-like glycosylation sites (PNGSs) in the V1 loop may have an impact on neutralizing activity. Understanding the mutations and evolution of MPER in chronically infected patients with HIV-1 is crucial for the design and development of vaccines that trigger bnAbs against MPER.</p></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168170224000704/pdfft?md5=95b3ae80d35226b71d340ab3f563bffc&pid=1-s2.0-S0168170224000704-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140682388","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}