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The immune response to SARS-CoV-2 in people with hiv

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Cellular & molecular Immunology 2024年第2期21卷 184-196页

作者： Maxine A.Höft Wendy A.Burgers Catherine Riou Institute of Infectious Disease and molecular Medicine University of Cape TownCape TownSouth Africa Division of Medical virology Department of PathologyUniversity of Cape TownCape TownSouth Africa Wellcome Centre for Infectious Diseases research in Africa University of Cape TownCape TownSouth Africa

This review examines the intersection of the hiv and SARS-CoV-2 *** with hiv(PWH)are a heterogeneous group that differ in their degree of immune suppression,immune reconstitution,and viral *** COVID-19 in those with wellcontrolled hiv infection poses no greater risk than that for hiv-uninfected individuals,people with advanced hiv disease are more vulnerable to poor COVID-19 ***-19 vaccines are effective and well tolerated in the majority of PWH,though reduced vaccine efficacy,breakthrough infections and faster waning of vaccine effectiveness have been demonstrated in *** is likely a result of suboptimal humoral and cellular immune responses after *** with advanced hiv may also experience prolonged infection that may give rise to new epidemiologically significant variants,but initiation or resumption of antiretroviral therapy(ART)can effectively clear persistent ***-19 vaccine guidelines reflect these increased risks and recommend prioritization for vaccination and additional booster doses for PWH who are moderately to severely *** recommend continued research and monitoring of PWH with SARS-CoV-2 infection,especially in areas with a high hiv burden.

关键词： SARS-CoV-2 hiv Immune dysfunction Vaccine efficacy Prolonged infection Immunogenicity

The V1 region of gp120 is preferentially selected during SIV/hiv transmission and is indispensable for envelope function and virus infection

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Virologica Sinica 2016年第3期31卷 207-218页

作者： Yanpeng Li Ulf Dittmer Yan Wang Jiping Song Binlian Sun Rongge Yang research group of hiv molecular epidemiology and virology Center for Emerging Infectious DiseasesState Key Laboratory of VirologyWuhan Institute of VirologyChinese Academy of Sciences Institute for virology University Hospital EssenUniversity of Duisburg-Essen

A transmission bottleneck occurs during each human immunodeficiency virus(hiv) transmission event, which allows only a few viruses to establish new infection. However, the genetic characteristics of the transmitted viruses that are preferentially selected have not been fully elucidated. Here, we analyzed amino acids changes in the envelope protein during simian immunodeficiency virus(SIV)/hiv deep transmission history and current hiv evolution within the last 15–20 years. Our results confirmed that the V1V2 region of gp120 protein, particularly V1, was preferentially selected. A shorter V1 region was preferred during transmission history, while during epidemic, hiv may evolve to an expanded V1 region gradually and thus escape immune recognition. We then constructed different hiv-1 V1 mutants using different hiv-1 subtypes to elucidate the role of the V1 region in envelope function. We found that the V1 region, although highly variable, was indispensable for virus entry and infection, probably because V1 deletion mutants exhibited impaired processing of gp160 into mature gp120 and gp41. Additionally, the V1 region affected Env incorporation. These results indicated that the V1 region played a critical role in hiv transmission and infection.

关键词： simian immunodeficiency virus(SIV) human immunodeficiency virus(hiv) transmission selection V1 loop Env function

TRIM22 Inhibits the TRAF6-stimulated NF-κB Pathway by Targeting TAB2 for Degradation

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Virologica Sinica 2013年第4期28卷 209-215页

作者： Hui Qiu Fang Huang Han Xiao Binlian Sun Rongge Yang research group of hiv molecular epidemiology and virology Center for Emerging Infectious Diseases The State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences

Tripartite motif containing 22 （TRIM22）, a member of the TRIM/RBCC family, has been reported to activate the nuclear factor-kappa B （NF-kB） pathway in unstimulated macrophage cell lines, but the detailed mechanisms governing this activation remains unclear. We investigated this mechanism in HEK293T cells. We found that overexpression of TRIM22 could activate the NF-kB pathway and conversely, could inhibit the tumor necrosis factor receptor-associated factor 6 （TRAF6）-stimulated NF-kB pathway in HEK293T cells. Further experiments showed that TRIM22 could decrease the self-ubiquitination of TRAF6, and interact with and degrade transforming growth factor-13 activated kinase 1 binding protein 2 （TAB2）, and that these effects could be partially rescued by a TRIM22 RING domain deletion mutant. Collectively, our data indicate that overexpression of TRIM22 may negatively regulate the TRAF6-stimulated NF-rd3 pathway by interacting with and degrading TAB2.

关键词： TRIM22 NF-kB pathway TRAF6 TAB2

Flux Balance Analysis Reveals Potential Anti-hiv-1 Metabolic Targets

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Infectious Diseases & Immunity 2024年第2期4卷 61-68页

作者： Runpeng Han Fei Luo Haisheng Yu Yajun Yan Yan Gong Conghua Xie Liang Cheng Department of Radiation and Medical Oncology Medical Research InstituteZhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430071China Frontier Science Center for Immunology and Metabolism Zhongnan Hospital of Wuhan UniversityState Key Laboratory of VirologyWuhan UniversityWuhan 430071China Guangzhou Eighth People's Hospital Guangzhou Medical UniversityGuangzhou 510440China Department of Infectious Diseases Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Wuhan research Center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Human immunodeficiency virus type 1(hiv-1)remains a persistent global health ***,a continuous exploration of novel therapeutic strategies is essential.A comprehensive understanding of how hiv-1 utilizes the cellular metabolism machinery for replication can provide insights into new therapeutic ***:In this study,we performed a flux balance analysis using a genome-scale metabolic model(GEM)integrated with an hiv-1 viral biomass objective function to identify potential targets for anti–hiv-1 *** generated a GEM by integrating an hiv-1 production reaction into CD4+T cells and optimized for both host and virus optimal states as objective functions to depict metabolic profiles of cells in the status for optimal host biomass maintenance or for optimal hiv-1 virion *** analysis was used to predict biochemical reactions altered optimal for hiv-1 *** addition,we conducted in silico simulations involving gene and reaction knock-outs to identify potential anti–hiv-1 targets,which were subsequently validated by human phytohemagglutinin(PHA)blasts infected with ***:Differential analysis identified several altered biochemical reactions,including increased lysine uptake and oxidative phosphorylation(OXPHOS)activities in the virus optima compared with the host *** silico gene and reaction knock-out simulations revealed de novo pyrimidine synthesis,and OXPHOS could serve as potential anti–hiv-1 metabolic *** vitro assay confirmed that targeting OXPHOS using metformin could suppress the replication of hiv-1 by 56.6%(385.4±67.5 pg/mL in the metformintreated group vs.888.4±32.3 pg/mL in the control group,Phiv therapies.

关键词： hiv-1 Flux balance analysis Genome-scale metabolic models Viral biomass objective function Therapeutic target

Complex positive selection pressures drive the evolution of hiv-1 with different co-receptor tropisms

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Science China(Life Sciences) 2010年第10期53卷 1204-1214页

作者： ZHANG ChiYu DING Na CHEN KePing YANG RongGe Institute of Life Sciences Jiangsu UniversityZhenjiang 212013China hiv molecular epidemiology and virology research group State Key Laboratory of VirologyWuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China

hiv-1 co-receptor tropism is central for understanding the transmission and pathogenesis of hiv-1 infection. We performed a genome-wide comparison between the adaptive evolution of R5 and X4 variants from hiv-1 subtypes B and C. The results showed that R5 and X4 variants experienced differential evolutionary patterns and different hiv-1 genes encountered various positive selection pressures, suggesting that complex selection pressures are driving hiv-1 evolution. Compared with other hypervariable regions of Gp120, significantly more positively selected sites were detected in the V3 region of subtype B X4 variants, V2 region of subtype B R5 variants, and V1 and V4 regions of subtype C X4 variants, indicating an association of positive selection with co-receptor recognition/binding. Intriguingly, a significantly higher proportion (33.3% and 55.6%, Phiv-1 variants, indicating that the C3 region might be more important to hiv-1 adaptation than previously thought. Approximately half of the positively selected sites identified in the env gene were identical between R5 and X4 variants. There were three common positively selected sites (96, 113 and 281) identified in Gp41 of all X4 and R5 variants from subtypes B and C. These sites might not only suggest a functional importance in viral survival and adaptation, but also imply a potential cross-immunogenicity between hiv-1 R5 and X4 variants, which has important implications for AIDS vaccine development.

关键词： hiv-1 co-receptor tropism adaptive evolution positively selected site R5 and X4 Gp120 epitopes

Drug resistance mutation profiles of the drug-nave and first-line regimen-treated hiv-1-infected population of Suzhou, China

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Virologica Sinica 2017年第4期32卷 271-279页

作者： Tingting Li Feng Qian Ting Yuan Weilu Xu Li Zhu Jinlong Huang Haiyan Wang Yueping Zhu Yinling Wang Xiaohong Li Saihong Gu Zhuqing Tan Hui Chen Xiangrong Luo Wei Zhu Weniuan Lu Ping Xu Ming Li Yuying Chen Yong Gao Rongge Yang Chuanwu Zhu Binlian Sun research group of hiv-1 molecular epidemiology and virology The State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences University of Chinese Academy of Sciences Division of hiv-1/AIDS the Fifth People's Hospital of Suzhou Department of Microbiology and Immunology Schulich School of Medicine & Dentistry University of Western Ontario

Little is known about the prevalence of drug-resistant mutations in hiv-1-positive individuals in Suzhou, China. To elucidate the transmitted drug resistance(TDR) and acquired drug resistance mutation(ADR) profiles, we collected blood specimens from 127 drug-naive and 117 first-line drugtreated hiv-1-infected individuals sampled from 2014 to 2016 in Suzhou. We successfully amplified po/fragments from 100 drug-naive and 20 drug-treated samples. We then determined the drugresistant mutations to protease(PR) and reverse-transcriptase(RT) inhibitors according to the Stanford drug resistance database. Overall, 11 and 13 individuals had transmitted(drug-naive group) and acquired(treated group) resistance mutations, respectively. Six transmitted drugresistant mutations were found, including two mutations(L33F and L76V) in the protease region and four(K70N/E and V179D/E) in the RT region. Only L76 V was a major mutation, and K70N/E and V179D/E are known to cause low-level resistance to RT inhibitors. All 13 treated participants who had major drug resistance mutations demonstrated intermediate to high resistance to efavirenz and nevirapine, and six had a treatment duration of less than three months. No major mutations to RT inhibitors were found, implying that the epidemic of transmitted resistance mutations was not significant in this area. Our results suggest that more frequent virus load and drug resistance mutation tests should be conducted for individuals receiving antiretroviral treatment, especially for newly treated patients. Our research provides insights into the occurrence of hiv-1 drug resistance in Suzhou and will help to optimize the treatment strategy for this population.

关键词： hiv-1 drug resistance mutation first-line regimen China

Identification of a novel hiv-1 intra-circulating recombinant form 01_AE in China: a descendant of the previously identified CRF01_AE transmission clusters 1 and 6

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Science China(Life Sciences) 2015年第7期58卷 724-726页

作者： NING ChuanYi LI XingGuang TANG WeiMing ZHOU Bo CAI WeiPing TUCKER Joseph D. Guangzhou Eighth People's Hospital & University of North Carolina and China Project research Center for Regenerative Medicine Guangxi Medical University hiv molecular epidemiology and virology research group State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences

Dear Editors,Here, we report a novel hiv-1 intra-circulating recombinant form 01_AE （intra-CRF01_AE： CRF01-1AE/CRF01-6AE） composed of CRF01_AE transmission clusters 1 and 6, which was identified in a heterosexual male from Fujian, with one breakpoint observed in the vif gene. The CRF01_AE region I （HXB2： 868-5184） of the recombinant clustered with CRF01_AE transmission cluster 1, which is mainly circulating among injection drug users （IDUs） and heterosexuals in southern and southwestern China, with the support of a 100% bootstrap value. The CRF01_AE region II （HXB2： 5185-9605） of the recombinant clustered with CRF01_AE transmission cluster 6, which mainly prevails among heterosexuals in southern China, with the support of a 100% bootstrap value. To our knowledge, this is the first detection of a novel hiv-1 intra-CRF01_AE recombinant form （CRF01-1_AE/CRF01-6_ AE） in Fujian, China, which indicates ongoing active hiv-1 transmission among heter- osexuals in this region.

关键词： hiv-1 传输集群识别重组后代 AE

Inference of Global hiv-1 Sequence Patterns and Preliminary FeatureAnalysis

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Virologica Sinica 2013年第4期28卷 228-238页

作者： Yan Wang Reda Rawi Daniel Hoffmann Binlian Sun Rongge Yang AIDS and hiv research group State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences research group for Bioinformatics Center for Medical Biology University of Duisburg-Essen

The epidemiology of hiv-1 varies in different areas of the world, and it is possible that this complexity may leave unique footprints in the viral genome. Thus, we attempted to find significant patterns in global hiv-1 genome sequences. By applying the rule inference algorithm RIPPER (Repeated Incremental Pruning to Produce Error Reduction) to multiple sequence alignments of Env sequences from four classes of compiled datasets, we generated four sets of signature patterns. We found that these patterns were able to distinguish southeastern Asian from non- southeastern Asian sequences with 97.5% accuracy, Chinese from non-Chinese sequences with 98.3% accuracy, African from non-African sequences with 88.4% accuracy, and southern African from non-southern African sequences with 91.2% accuracy. These patterns showed different associations with subtypes and with amino acid positions. In addition, some signature patterns were characteristic of the geographic area from which the sample was taken. Amino acid features corresponding to the phylogenetic clustering of hiv-1 sequences were consistent with some of the deduced patterns. Using a combination of patterns inferred from subtypes B, C, and all subtypes chimeric with CRF01_AE worldwide, we found that signature patterns of subtype C were extremely common in some sampled countries (for example, Zambia in southern Africa), which may hint at the origin of this hiv-1 subtype and the need to pay special attention to this area of Africa. Signature patterns of subtype B sequences were associated with different countries. Even more, there are distinct patterns at single position 21 with glycine, leucine and isoleucine corresponding to subtype C, B and all possible recombination forms chimeric with CRF01_AE, which also indicate distinct geographic features. Our method widens the scope of inference of signature from geographic, genetic, and genomic viewpoints. These findings may provide a valuable reference for epidemiological resea

关键词： Pattern inference global hiv- 1 sequence Repeated Incremental Pruning to Produce Error Reduction (RIPPER)

Differential selection in hiv-1 gp120 between subtype B and East Asian variant B'

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Virologica Sinica 2014年第1期29卷 40-47页

作者： Stefan Dang Yan Wang Bettina Budeus Jens Verheyen Rongge Yang Daniel Hoffmann research group Bioinformatics Center of Medical Biotechnology and Faculty of BiologyUniversity of Duisburg-Essen AIDS and hiv research group State Key Laboratory of VirologyWuhan Institute of VirologyChineseAcademy of Sciences Institute of virology University of Duisburg-Essen

hiv-1 evolves strongly and undergoes geographic differentiation as it spreads in diverse host populations around the *** instance,distinct genomic backgrounds can be observed between the pandemic subtype B,prevalent in Europe and North-America,and its offspring clade B＇ in East *** we ask whether this differentiation affects the selection pressure experienced by the *** answer this question we evaluate selection pressure on the hiv-1 envelope protein gp120 at the level of individual codons using a simple and fast estimation method based on the ratio ka/ks of amino acid changes to synonymous *** validate the approach we compare results to those from a state-of-the-art mixed-effect *** agreement is acceptable,but the analysis also demonstrates some limitations of the simpler ***,we find similar distributions of codons under stabilizing and directional selection pressure in gp120 for subtypes B and B＇ with more directional selection pressure in variable loops and more stabilizing selection in the constant *** on codons with increased ka/ks values in B＇,we show that these codons are scattered over the whole of gp120,with remarkable clusters of higher density in regions flanking the variable *** identify a significant statistical association of glycosylation sites and codons with increased ka/ks values.

关键词： human immunodeficiency virus 1 selection pressure genomic background