RESEARCH ARTICLE
Emergence of CXCR4-tropic HIV-1 variants followed by rapid disease progression in hemophiliac slow progressors Tsunefusa Hayashida1, Kiyoto Tsuchiya1, Yoshimi Kikuchi1, Shinichi Oka1,2, Hiroyuki Gatanaga1,2* 1 AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan, 2 Center for AIDS Research, Kumamoto University, Kumamoto, Japan
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* [email protected]
Abstract Objective
OPEN ACCESS Citation: Hayashida T, Tsuchiya K, Kikuchi Y, Oka S, Gatanaga H (2017) Emergence of CXCR4-tropic HIV-1 variants followed by rapid disease progression in hemophiliac slow progressors. PLoS ONE 12(5): e0177033. https://doi.org/ 10.1371/journal.pone.0177033 Editor: Fabrizio Mammano, "INSERM", FRANCE Received: January 24, 2017 Accepted: April 20, 2017 Published: May 4, 2017 Copyright: © 2017 Hayashida et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All sequence files are available from DNA Data Bank of Japan (accession numbers LC225774-LC227557). Funding: This work was supported by a Grant for National Center for Global Health and Medicine [28SI-1102]; and a Grant from the Japan Agency for Medical Research and Development (AMED) [AIDS-H26]), which were received by HG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The association between emergence of CXCR4-tropic HIV-1 variants (X4 variants) and disease progression of HIV-1 infection has been reported. However, it is not known whether the emergence of X4 variants is the cause or result of HIV-1 disease progression. We tried to answer this question.
Design HIV-1 env sequences around the V3 region were analyzed in serially stocked samples in order to determine whether X4 variants emerged before or after the fall in CD4+ T-cell count.
Methods The study subjects were five HIV-1-infected hemophiliac slow progressors. Deep sequencing around the HIV-1 env V3 region was conducted in duplicate. Tropism was predicted by geno2pheno [coreceptor] 2.5 with cutoff value of false positive ratio at
Emergence of CXCR4-tropic HIV-1 variants followed by rapid disease progression in hemophiliac slow progressors Tsunefusa Hayashida1, Kiyoto Tsuchiya1, Yoshimi Kikuchi1, Shinichi Oka1,2, Hiroyuki Gatanaga1,2* 1 AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan, 2 Center for AIDS Research, Kumamoto University, Kumamoto, Japan
a1111111111 a1111111111 a1111111111 a1111111111 a1111111111
* [email protected]
Abstract Objective
OPEN ACCESS Citation: Hayashida T, Tsuchiya K, Kikuchi Y, Oka S, Gatanaga H (2017) Emergence of CXCR4-tropic HIV-1 variants followed by rapid disease progression in hemophiliac slow progressors. PLoS ONE 12(5): e0177033. https://doi.org/ 10.1371/journal.pone.0177033 Editor: Fabrizio Mammano, "INSERM", FRANCE Received: January 24, 2017 Accepted: April 20, 2017 Published: May 4, 2017 Copyright: © 2017 Hayashida et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All sequence files are available from DNA Data Bank of Japan (accession numbers LC225774-LC227557). Funding: This work was supported by a Grant for National Center for Global Health and Medicine [28SI-1102]; and a Grant from the Japan Agency for Medical Research and Development (AMED) [AIDS-H26]), which were received by HG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The association between emergence of CXCR4-tropic HIV-1 variants (X4 variants) and disease progression of HIV-1 infection has been reported. However, it is not known whether the emergence of X4 variants is the cause or result of HIV-1 disease progression. We tried to answer this question.
Design HIV-1 env sequences around the V3 region were analyzed in serially stocked samples in order to determine whether X4 variants emerged before or after the fall in CD4+ T-cell count.
Methods The study subjects were five HIV-1-infected hemophiliac slow progressors. Deep sequencing around the HIV-1 env V3 region was conducted in duplicate. Tropism was predicted by geno2pheno [coreceptor] 2.5 with cutoff value of false positive ratio at
