HIV-1 Nef和gag变异与宿主HLA特征作为肯尼亚HIV-1垂直感染儿童疾病进展决定因素的比较

Comparison of HIV-1 nef and gag Variations and Host HLA Characteristics as Determinants of Disease Progression among HIV-1 Vertically Infected Kenyan Children.

作者信息

Saina Matilda Chelimo, Bi Xiuqiong, Lihana Raphael, Lwembe Raphael, Ishizaki Azumi, Panikulam Annie, Palakudy Tresa, Musoke Rachel, Owens Mary, Songok Elijah Maritim, Ichimura Hiroshi

机构信息

Department of Viral Infection and International Health, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.

Center for Virus Research, Kenya Medical Research Institute, Nairobi, Kenya.

出版信息

PLoS One. 2015 Aug 28;10(8):e0137140. doi: 10.1371/journal.pone.0137140. eCollection 2015.

DOI:10.1371/journal.pone.0137140

PMID:26317223

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4552823/

Abstract

OBJECTIVES

Disease progression varies among HIV-1-infected individuals. The present study aimed to explore possible viral and host factors affecting disease progression in HIV-1-infected children.

METHODS

Since 2000, 102 HIV-1 vertically-infected children have been followed-up in Kenya. Here we studied 29 children (15 male/14 female) who started antiretroviral treatment at <5 years of age (rapid progressors; RP), and 32 (17 male/15 female) who started at >10 years of age (slow progressors; SP). Sequence variations in the HIV-1 gag and nef genes and the HLA class I-related epitopes were compared between the two groups.

RESULTS

Based on nef sequences, HIV-1 subtypes A1/D were detected in 62.5%/12.5% of RP and 66.7%/20% of SP, with no significant difference in subtype distribution between groups (p = 0.8). In the ten Nef functional domains, only the PxxP3 region showed significantly greater variation in RP (33.3%) than SP (7.7%, p = 0.048). Gag sequences did not significantly differ between groups. The reportedly protective HLA-A alleles, A74:01, A32:01 and A26, were more commonly observed in SP (50.0%) than RP (11.1%, p = 0.010), whereas the reportedly disease-susceptible HLA-B45:01 was more common in RP (33.3%) than SP (7.4%, p = 0.045). Compared to RP, SP showed a significantly higher median number of predicted HLA-B-related 12-mer epitopes in Nef (3 vs. 2, p = 0.037), HLA-B-related 11-mer epitopes in Gag (2 vs. 1, p = 0.029), and HLA-A-related 9-mer epitopes in Gag (4 vs. 1, p = 0.051). SP also had fewer HLA-C-related epitopes in Nef (median 4 vs. 5, p = 0.046) and HLA-C-related 11-mer epitopes in Gag (median 1 vs. 1.5, p = 0.044) than RP.

CONCLUSIONS

Compared to rapid progressors, slow progressors had more protective HLA-A alleles and more HLA-B-related epitopes in both the Nef and Gag proteins. These results suggest that the host factor HLA plays a stronger role in disease progression than the Nef and Gag sequence variations in HIV-1-infected Kenyan children.

摘要

目的

HIV-1感染个体的疾病进展情况各不相同。本研究旨在探索影响HIV-1感染儿童疾病进展的可能病毒和宿主因素。

方法

自2000年以来，肯尼亚对102名HIV-1垂直感染儿童进行了随访。在此，我们研究了29名在5岁前开始抗逆转录病毒治疗的儿童（快速进展者；RP）和32名在10岁后开始治疗的儿童（缓慢进展者；SP）。比较了两组之间HIV-1 gag和nef基因的序列变异以及HLA I类相关表位。

结果

基于nef序列，在62.5%/12.5%的RP中检测到HIV-1 A1/D亚型，在66.7%/20%的SP中检测到该亚型，两组间亚型分布无显著差异（p = 0.8）。在Nef的十个功能域中，只有PxxP3区域在RP中的变异（33.3%）显著高于SP（7.7%，p = 0.048）。两组间gag序列无显著差异。据报道具有保护作用的HLA-A等位基因A74:01、A32:01和A26在SP中（50.0%）比RP中（11.1%，p = 0.010）更常见，而据报道易患疾病的HLA-B45:01在RP中（33.3%）比SP中（7.4%，p = 0.045）更常见。与RP相比，SP在Nef中预测的HLA-B相关12聚体表位中位数显著更高（3对2，p = 0.037），在Gag中HLA-B相关11聚体表位中位数更高（2对1，p = 0.029），在Gag中HLA-A相关9聚体表位中位数更高（4对1，p = 0.051）。SP在Nef中HLA-C相关表位也比RP少（中位数4对5，p = 0.046），在Gag中HLA-C相关11聚体表位也比RP少（中位数1对1.5，p = 0.044）。