Covariability of selected amino acid positions for HIV type 1 subtypes C and B
Covariability of selected amino acid positions for HIV type 1 subtypes C and B
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DOI：
10.1089/aid.2005.21.1016
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发表时间：
2005-12-01
影响因子：
1.5
通讯作者：
Essex, M
中科院分区：
文献类型：
--
作者：
Gilbert, PB;Novitsky, V;Essex, M
我们研究了全球占主导地位的HIV-1亚型C病毒中选定的氨基酸位置的协变性。分析的序列跨越V3环、Gag p17、Gag p24和Gag、Nef和达特中的五个CTL表位富集区。对HIV-1亚型B的相应区域进行了评价。这些分析鉴定了HIV-1B V3环中大量的共变对和三联位点（173个位点对，242个位点三联体）。在早期的研究中发现了其中的几种相互作用[例如，Korber等（Proc Natl Acad Sci USA 1993; 90：7176-7180）和Bickel等（AIDS Res Res Retroviruses 1996; 12：1，4011411）的V3环共变分析]，并具有已知的生物学意义。然而，通常这些关键的共变位点在HIV-1C V3环中没有共变（总共17个共变位点对），这表明V3环在功能或结构操作特征上可能具有亚型差异。在免疫显性区域HIV-1C Gag 291-320中观察到位置309和312的协变，但在HIV-1B的相应区域中未发现协变，Nef 122-141反之亦然;这些发现可能反映了免疫相关区域内的亚型特异性协变。Gag p17在H1 V-1B中表现出比HIV-1C更大的协变性和更少的多样性，提出了Gag p17在HIV-1B中高度免疫显性的假设，并且对于HIV-1B疫苗特别重要。在评估HIV-1多样性以及如何通过疫苗设计克服这种多样性时，应更好地利用关于协变性的信息。
We studied covariability of selected amino acid positions in globally dominant HIV-1 subtype C viruses. The analyzed sequences spanned the V3 loop, Gag p17, Gag p24, and five CTL epitope-rich regions in Gag, Nef, and Tat. The corresponding regions in HIV-1 subtype B were also evaluated. The analyses identified a great number of covarying pairs and triples of sites in the HIV-1B V3 loop (173 site pairs, 242 site triples). Several of these interactions were found in the earlier studies [e.g., the V3 loop covariability analyses by Korber et al. (Proc Natl Acad Sci USA 1993; 90:7176-7180) and Bickel et al. (AIDS Res Hum Retroviruses 1996; 12:1,4011411)] and have known biological significance. However, generally these key covarying sites did not covary in the HIV-1C V3 loop (total 17 covarying site pairs), suggesting that the V3 loop may have subtype differences in functional or structural operating characteristics. Covariability of positions 309 and 312 was observed in the immunodominant region HIV-1C Gag 291-320 but no covariability was found in the corresponding region of HIV-1B, and vice versa for Nef 122-141; these findings may reflect subtype-specific covariability within immunologically relevant regions. Gag p17 exhibited greater covariability and less diversity for H1V-1B than HIV-1C, raising the hypothesis that Gag p17 is highly immunodominant in HIV-1B and is especially important for HIV-1B vaccines. Information on covariability should be better exploited in assessments of HIV-1 diversity and how to surmount it with vaccine design.