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      The dynamics of the HIV epidemic among men who have sex with men (MSM) from 2005 to 2012 in Shenzhen, China

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          Abstract

          HIV-1 epidemics among MSM are a major public health concern in China, especially in large cities. This study sought to better understand the dynamics of HIV molecular epidemiology among MSM in Shenzhen, a rapidly developing city with over 13.8 million people. HIV-1 pol sequences were obtained from 996 (53.5%) of 1862 HIV-infected MSM and 403(9.0%) of 4498 heterosexuals and injection drug users in Shenzhen, China from 2005-2012. Eight HIV-1 subtypes and some inter-subtype recombinants were identified among sampled MSM with CRF07_BC (39.1%) and CRF01_AE (35.1%) being the most predominant. From 2006 to 2012, the prevalence of CRF07_BC and CRF55_01B rapidly increased, while the prevalence of subtypes B and CRF01_AE gradually decreased. The genetic distances within CRF07_BC and CRF55_01B groups were significantly lower than within CRF01_AE and B groups. The vast majority (90.3%) of HIV-1 infected MSM in Shenzhen were migrants who came from 31 of the 34 provinces of China, and these migrants had significantly different HIV-1 subtype distributions from the local MSM. This study highlighted the importance of CRF07_BC and migrants in the changing HIV epidemic among MSM in China, and provides a molecular epidemiology framework for understanding how HIV-1 epidemics can change in large cities with diverse risk groups.

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          Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination.

          The development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. In addition, full-genome data are particularly limited for HIV-1 subtype C, currently the most commonly transmitted subtype in India and worldwide. Likewise, little is known about sequence variation of HIV-1 in India, the country facing the largest burden of HIV worldwide. Therefore, the objective of this study was to clone and characterize the complete genome of HIV-1 from seroconverters infected with subtype C variants in India. Cocultured HIV-1 isolates were obtained from six seroincident individuals from Pune, India, and virtually full-length HIV-1 genomes were amplified, cloned, and sequenced from each. Sequence analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env, nef, and the 3' long terminal repeat as determined by both maximal chi2 analysis and phylogenetic bootstrapping. Sequences were compared for preservation of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-1LAI sequence, 38% of well-defined CTL epitopes were identical. The proportion of nonconservative substitutions for Env, at 61%, was higher (P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, characterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env. Because these clones were obtained from Indian seroconverters, they are likely to facilitate vaccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness.
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            Evolutionary distance estimation under heterogeneous substitution pattern among lineages.

            Most of the sophisticated methods to estimate evolutionary divergence between DNA sequences assume that the two sequences have evolved with the same pattern of nucleotide substitution after their divergence from their most recent common ancestor (homogeneity assumption). If this assumption is violated, the evolutionary distance estimated will be biased, which may result in biased estimates of divergence times and substitution rates, and may lead to erroneous branching patterns in the inferred phylogenies. Here we present a simple modification for existing distance estimation methods to relax the assumption of the substitution pattern homogeneity among lineages when analyzing DNA and protein sequences. Results from computer simulations and empirical data analyses for human and mouse genes are presented to demonstrate that the proposed modification reduces the estimation bias considerably and that the modified method performs much better than the LogDet methods, which do not require the homogeneity assumption in estimating the number of substitutions per site. We also discuss the relationship of the substitution and mutation rate estimates when the substitution pattern is not the same in the lineages leading to the two sequences compared.
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              A computer program designed to screen rapidly for HIV type 1 intersubtype recombinant sequences.

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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                29 June 2016
                2016
                : 6
                : 28703
                Affiliations
                [1 ]Shenzhen Center for Disease Control and Prevention , Shenzhen, China
                [2 ]University of California San Diego , La Jolla, California, USA
                [3 ]Veterans Affairs Healthcare System San Diego , San Diego, California, USA
                [4 ]Pathogen Diagnostic Center, Institut Pasteur of Shanghai, Chinese Academy of Sciences , Shanghai, China
                [5 ]Shanghai Municipal Center for Disease Control and Prevention , Shanghai, China
                Author notes
                [*]

                These authors contributed equally to this work.

                Article
                srep28703
                10.1038/srep28703
                4926087
                27352965
                57216ab8-a93c-479c-bdfe-f4c22ae8ab7f
                Copyright © 2016, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 31 March 2016
                : 06 June 2016
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