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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

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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%, P120 in all the analyzed hiv-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

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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

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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

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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

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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)

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Emergence of a New hiv-1 CRFO1AE Variant in Guangxi,Southern China

Emergence of a New HIV-1 CRFO1AE Variant in Guangxi,Southern...

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第五届全国生物信息学与系统生物学学术大会暨国际生物信息学前沿研讨会高通量时代的生物信息学与系统生物学

作者： Haiyan Zeng Zhiwu Sun Shujia Liang Lingnuo Li Yanyan Jiang Wei Liu Binlian Sun Jingyun Li Rongge Yang research group of hiv molecular epidemiology and virology The State Key Laboratory of VirologyWuhan Institution of VirologyChinese Academy of Sciences Guangxi Province Center for Disease Prevention and Control NanningGuangxi 530028The People's Republic of China Department of AIDS research The State Key Laboratory of Pathogen and BiosecurityBeijing Institute of Microbiology and Epidemiology

Background:Recent years’ reports in Guangxi showed that CRFO1AE had dominated in the central city Nanning and the eastern city Liuzhou,and there may be more than one introductions of CRF01E in *** gain a deeper understanding on the evolution of the hiv-1 epidemic and genetic characterization of CRFO1E in Guangxi,we recruited 349 hiv/AIDS patients from the cities all over Guangxi. Methods:Full-length gag,pol genes and partial env gene were amplified and analyzed using phylogenetic,recombinant,intersubject diversity,signature pattern,and sequence logo approaches. Results:The distribution of hiv-1 genotypes based on gag,pol and partial env sequences(n=349) was as follows:CRFO1E(66.5%),CRF08BC(19.2%),CRF07C (7.2%),URF(4.6%),subtype B(1.7%),and subtype B’(0.9%).CRF01AE predominated in all geographical regions and risk populations and there were multiple introductions of CRF01AE strains in *** found a peculiar CRF01E monophyletic lineage distinct from other CRF01E viruses,and we designated it "CRF01E-v" for ***01AE-v circulating in both heterosexuals and injecting drug users(IDUs) had accounted for 39.7%) of *** showed a selective advantage in the Guangxi population and formed its own characteristic compared with all the CRF01E references. Conclusions:Our results suggested that CRF01E-v was a new variant of CRF01E and it might lead to a new epidemic in Guangxi.

关键词： hiv-1 CRF01AE China signature pattern CRF0lAE-v

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hiv/AIDS in Asia:The Shape of Epidemics and Their molecular epidemiology

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Virologica Sinica 2007年第6期22卷 426-433页

作者： Rie Uenishi Saiki Hase Tee Kok Keng Shigeru Kusagawa Yutaka Takebe Laboratory of molecular virology and epidemiology AIDS Research CenterNational Institute of Infectious Diseases1-23-1 ToyamaShinjuku-kuTokyo 162-8640TokyoJapan

The Asia-Pacific region is a home to 60% of the population in the world and to approximately one quarter of people with hiv/AIDS. Close to a million of people has been infected and a half million people died of AIDS annually in Asia,becoming the second largest epicenter of global AIDS epidemic. molecular epidemiology has been useful tool to track a course of hiv spread. In-depth knowledge from the studies on molecular epidemiology elucidates the dynamics of hiv spread and the interrelationship of epidemics in the different regions in Asia.

关键词： molecular epidemiology Genetic variability Circulation recombinant form (CRF) Unique recombinant form (URF)

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group A Rotavirus Genotypes among Calf Herds in Southwest Nigeria and Implications for Human Rotavirus Vaccines’ Efficiency

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Open Journal of Veterinary Medicine 2020年第1期10卷 1-13页

作者： Michael Oluyemi Babalola epidemiology Molecular Virology and Special Pathogens Research Department of Microbiology Adekunle Ajasin University Akungba Akoko Ondo state Nigeria

Rotaviruses have been widely reported to be associated with diarrhea in humans but fewer studies abound on other mammalian species. This prospective study was conducted to detect and characterize Rotaviruses from freely ranged migratory herds of cattle in Ekiti and Ondo states, Nigeria with a view to further expanding knowledge on rotaviruses, possible animal-human interspecies transmission and impacts on vaccine efficiency. By convenience sampling, between September 2014 and February 2015, stool samples from 120 calves, comprising settled and migratory herds of cattle were obtained and examined for group A rotaviruses using Certest? Quadruple Enzyme Immuno Assay. Rotavirus genomes were isolated by extraction from the positive samples, reverse transcribed and amplified by One-Step reverse transcription polymerase chain reaction (RT-PCR), and genotyped by semi-nested multiplex PCR. Representative PCR products of the genotyped samples were purified and sequenced using Sanger method. The generated query sequences were queried to the GenBank to retrieve similar sequences for pairwise alignment by ClustalW. Phylogenetic analyses by Neighbour-joining method were conducted at 1000 bootstrap replicates to obtain phylograms using MEGA 6 software. Fifteen samples (15/120: 12.5%) were positive for rotavirus. No statistically significant association existed between rotavirus infection and gender of the calves (χ2 = 0, df = 1, p = 1). Eight samples (8/15: 53.3%) were successfully genotyped where the G1, G5, G9, G10, G12, and P[6] were detected. Nucleotide Sequencing of the VP7 and VP4 genes of the genotyped samples confirmed strains G1P[6], G10P[6], and G12P[6] with 58% - 100% nucleotide identity within these viruses. Phylogenetic analysis revealed 2 possible transmissions from India and Honduras. Bovine rotaviruses were detected in freely ranged and settled calf herds in southwestern Nigeria at a rate of 12.5%. The strains identified were analysed to be group A rotavirus strain

关键词： group A Rotavirus Diarrhea Calves Genotypes Vaccines

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Activity of superior interferon α against hiv-1 in severe combined immunodeficient mice reconstituted with human peripheral blood leukocytes

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Chinese Medical Journal 2011年第3期000卷 396-400页

作者： ZHANG Wei TONG Xiao Tadashi Nakasone YUE Xue-tian Naoki Yamamoto LIU Xin-yuan YANG Rong-ge Laboratory of hiv molecular epidemiology and virology State Key Laboratory of Virology Wuhan Institution of VirologyChinese Academy of Sciences Wuhan Hubei 430071 China AIDS research Center National Institute of Infectious Diseases1-23-1 Toyama Shinjuku-ku Tokyo 162-8640 Japan Zhejiang Sci-Tech University Hangzhou Zhejiang 310018 China Zhejiang Sci-Tech University Hangzhou Zhejiang 310018 China Laboratory of molecular Cell Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological SciencesChinese Academy of Sciences Shanghai 200031 China

Background Interferon （IFN） can inhibit human immunodeficiency virus type 1 （hiv-1） replication in vitro and in ***, IFN therapy for hiv infection was limited by its moderate antiviral efficacy and its frequent adverse effects. In the present study we evaluated the anti-hiv efficacy of a novel synthesized superior interferon α （slFNα）.Methods We performed in vitro experiments with hiv-1 IIB infected MT4 cells, and evaluated in vivo anti-hiv efficacy of slFNα in severe combined immunodeficient （SClD） mice reconstituted with human peripheral blood leukocytes （hu-PBL-SClD mice）.Results We found that the 50% effective concentrations （EC5o） of slFNα against the replication of hiv-1 in MT4 cells was 0.06 ng/ml, representing stronger antiviral activity than interferon-α in vitro. In the hu-PBL-SCID mice, a dose-dependent protection pattern was observed： with 0.45 μg and 1.35 μg slFNα daily treatments, parts of SCID mice were protected from hiv infection, whereas 2.25 μg sIFNα daily treatments resulted in a terminally complete *** slFNα shows good anti-hiv activity both in vitro and in SCID mice, may be a promising anti-hiv agent deserving clinical investigation, especially considering the potential of IFN-α to inhibit hiv replication in patients infected with drug-resistant variants or co-infected with hepatitis C virus （HCV）.

关键词： human immunodeficiency virus type 1 severe combined immunodeficient mouse interferon-α

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