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巴巴多斯1型人类免疫缺陷病毒B亚型感染的分子流行病学及耐药性测定

The molecular epidemiology and drug resistance determination of HIV type 1 subtype B infection in Barbados.

作者信息

Gittens Marquita V, Roth William W, Roach Timothy, Stringer H Gene, Pieniazek Danuta, Bond Vincent C, Levett Paul N

机构信息

School of Clinical Medicine and Research, University of the West Indies, Barbados.

出版信息

AIDS Res Hum Retroviruses. 2003 Apr;19(4):313-9. doi: 10.1089/088922203764969519.

Abstract

To better understand the emergence of HIV-1 variants in Barbados and the association with transmission modes, we analyzed phylogenetic relationships and genetic variability among HIV-1 strains collected in 1996 from 36 antiretroviral therapy-naive patients. Only subtype B variants were present in this sampling, based on analysis of HIV-1 envelope (env) C2V3, protease (PR), and reverse transcriptase (RT) sequences. The genetic diversity of env sequences was broad (13.9%; range, 5.9-24.9%), suggesting multiple introductions of distinct HIV-1 strains to the island. The frequency of subtype B HIV-1 variants with similar env V3 features, including the tetrameric tips, GPGR and GPGK, the threonine deletion at position 23, and the substitution of threonine to arginine at position 22, was comparable in heterosexual, bisexual, and homosexual patients. Analyses of amino acid variations in PR sequences revealed a lack of major drug resistance-conferring mutations and a high (90%) prevalence of secondary mutations at positions 36, 63, 71, and 77. While the occurrence of 361, 63P, and 71T mutations in Barbadian strains was similar to the global prevalence for subtype B variants, the frequency (64%) of the V77I mutation was more than three times that seen worldwide. Only two RT antiretroviral resistance mutations (M41L and T215Y) were observed, both from a single patient. This comprehensive genetic analysis documents a broad diversity within HIV-1 subtype B in Barbados and suggests a lack of association between particular subtype B variants and transmission modes.

摘要

为了更好地了解巴巴多斯岛HIV-1变体的出现情况以及与传播方式的关联,我们分析了1996年从36名未接受过抗逆转录病毒治疗的患者中收集的HIV-1毒株之间的系统发育关系和基因变异性。基于对HIV-1包膜(env)C2V3、蛋白酶(PR)和逆转录酶(RT)序列的分析,该样本中仅存在B亚型变体。env序列的基因多样性广泛(13.9%;范围为5.9 - 24.9%),表明不同的HIV-1毒株多次传入该岛。具有相似env V3特征(包括四聚体末端、GPGR和GPGK、23位苏氨酸缺失以及22位苏氨酸替换为精氨酸)的B亚型HIV-1变体在异性恋、双性恋和同性恋患者中的频率相当。对PR序列中氨基酸变异的分析显示,缺乏主要的耐药性突变,并且在36、63、71和77位存在较高(90%)的二级突变发生率。虽然巴巴多斯毒株中36I、63P和71T突变的发生率与B亚型变体的全球流行率相似,但V77I突变的频率(64%)是全球范围内观察到的频率的三倍多。仅观察到两个RT抗逆转录病毒耐药性突变(M41L和T215Y),均来自一名患者。这项全面的基因分析记录了巴巴多斯岛HIV-1 B亚型内的广泛多样性,并表明特定的B亚型变体与传播方式之间缺乏关联。

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