人类白细胞抗原相关的Pol和Gag突变与HIV-1 A/E亚型感染临床参数之间的强烈关联。

A strong association of human leukocyte antigen-associated Pol and Gag mutations with clinical parameters in HIV-1 subtype A/E infection.

作者信息

Van Tran Giang, Chikata Takayuki, Carlson Jonathan M, Murakoshi Hayato, Nguyen Dung Hoai, Tamura Yoshiko, Akahoshi Tomohiro, Kuse Nozomi, Sakai Keiko, Sakai Sachiko, Cobarrubias Kyle, Oka Shinichi, Brumme Zabrina L, Van Nguyen Kinh, Takiguchi Masafumi

机构信息

aCenter for AIDS Research, Kumamoto University, Kumamoto, Japan beScience Group, Microsoft Research, Los Angeles, California, USA cNational Hospital of Tropical Diseases, Dong Da District, Hanoi, Vietnam dFaculty of Health Sciences, Simon Fraser University, Burnaby, BC, USA eAIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan fBritish Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada gInternational Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan hNuffield Department of Medicine, University of Oxford, Oxford, UK. *Giang Van Tran and Takayuki Chikata contributed equally to this study.

出版信息

AIDS. 2016 Mar 13;30(5):681-9. doi: 10.1097/QAD.0000000000000969.

DOI:10.1097/QAD.0000000000000969

PMID:26595539

Abstract

OBJECTIVES

Identification of human leukocyte antigen-associated HIV-1 polymorphisms (HLA-APs) in different global populations furthers our understanding of HIV-1 pathogenesis and may help identify candidate immunogens for HIV vaccines targeted to these populations. Although numerous population-based studies identifying HLA-APs have been conducted in HIV-1 subtype B- and subtype C-infected cohorts, few have focused on subtype A/E.

DESIGN

We investigated HLA-APs in a cohort of chronically HIV-1 subtype A/E-infected Vietnamese individuals.

METHODS

HLA-APs in HIV-1 Gag, Pol, and Nef regions from 388 treatment-naive individuals chronically infected with HIV-1 subtype A/E were analyzed using phylogenetically informed approaches.

RESULTS

A total of 303 HLA-APs were identified. HLA-APs occurring at six positions in Gag and six positions in Pol were significantly associated with higher plasma viral load (pVL), whereas HLA-APs occurring at two positions in Gag and 13 positions in Pol were significantly associated with lower CD4 T-cell counts. Furthermore, the proportion of Pol codons harboring an HLA-AP specific to the host's HLA correlated positively with HIV-1 pVL (R = 0.22; P < 0.0001) and inversely with CD4 T-cell counts (R = -0.32; P < 0.0001). Similarly, the proportion of HLA-associated Gag codons harboring host-specific HLA-AP correlated inversely with CD4 T-cell counts (R = -0.13; P = 0.01).

CONCLUSION

These significant associations between HIV-1 amino acids adapted to Vietnamese HLA alleles and higher pVL and lower CD4 T-cell counts suggests that accumulation of cytotoxic T cells escape mutations may influence clinical outcomes in HIV-1 subtype A/E-infected Vietnamese individuals.

摘要

目的

鉴定不同全球人群中与人类白细胞抗原相关的HIV-1多态性（HLA-APs），有助于我们进一步了解HIV-1发病机制，并可能有助于识别针对这些人群的HIV疫苗的候选免疫原。尽管已在HIV-1 B亚型和C亚型感染队列中开展了大量基于人群的研究来鉴定HLA-APs，但很少有研究关注A/E亚型。

设计

我们调查了一组长期感染HIV-1 A/E亚型的越南个体中的HLA-APs。

方法

采用系统发育信息方法分析了388例未经治疗的长期感染HIV-1 A/E亚型个体的HIV-1 Gag、Pol和Nef区域中的HLA-APs。

结果

共鉴定出303个HLA-APs。Gag区域六个位置和Pol区域六个位置出现的HLA-APs与较高的血浆病毒载量（pVL）显著相关，而Gag区域两个位置和Pol区域13个位置出现的HLA-APs与较低的CD4 T细胞计数显著相关。此外，携带宿主HLA特异性HLA-AP的Pol密码子比例与HIV-1 pVL呈正相关（R = 0.22；P < 0.0001），与CD4 T细胞计数呈负相关（R = -0.32；P < 0.0001）。同样，携带宿主特异性HLA-AP的HLA相关Gag密码子比例与CD4 T细胞计数呈负相关（R = -......