Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination
Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination
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DOI：
10.1128/jvi.73.1.152-160.1999
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发表时间：
1999-01-01
影响因子：
5.4
通讯作者：
Ray, SC
中科院分区：
文献类型：
--
作者：
Lole, KS;Bollinger, RC;Ray, SC
开发一种有效的人类免疫缺陷病毒I型(HIV-1)疫苗可能取决于对通常测序的Gag和env基因以外的基因的循环变异的了解。此外，关于艾滋病毒-1 C亚型的全基因组数据尤其有限，这是目前在印度和世界范围内最常见的传播亚型。印度是世界上HIV感染负担最大的国家，与印度一样，人们对HIV-1的序列变异知之甚少，因此，本研究的目的是从印度感染C亚型变异的血清转换者中克隆和鉴定HIV-1的全基因组。共培养的HIV-1分离株来自印度浦那的六个血清事件个体，并从每个分离株扩增、克隆和测序了几乎全长的EIN-I基因组。序列分析表明，6个基因组中有5个是C亚型，1个是A和C亚型的嵌合体，最大X_1(2)分析和系统发育自举分析都确定了env、nef和3‘端长重复序列的多个断裂点。对已知的细胞毒性T淋巴细胞(CTL)表位的保存进行了序列比较。与HIV-I序列相比，38%的明确CTL表位是相同的。Env的非保守替换比例为61%(P<；0.001)，高于Gag(24%)、POL(18%)和Nef(32%)。因此，特征化的CTL表位与在环境病毒中最明显的B亚型实验室毒株显示出显著的差异，因为这些克隆来自印度的血清转换者，它们可能通过为疫苗候选者以及疫苗反应性测试提供潜在抗原而促进印度的疫苗相关工作。
The development of an effective human immunodeficiency virus type I (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. In addition, full-genome data are particularly limited for HIV-1 subtype C, currently the most commonly transmitted subtype in India and worldwide. Like,,ise, little is known about sequence variation of HIV-1 in India, the country facing the largest burden of HIV worldwide, Therefore, the objective of this study was to clone and characterize the complete genome of HIV-1 from seroconverters infected with subtype C variants in India. Cocultured HIV-1 isolates were obtained from six seroincident individuals from Pune, India, and virtually full-length EIN-I genomes were amplified, cloned, and sequenced from each. Sequence analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env, nef, and the 3' long terminal repeat as determined by both maximal chi(2) analysis and phylogenetic bootstrapping. Sequences were compared for preservation of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-I, sequence, 38% of well-defined CTL epitopes were identical. The proportion of nonconservative substitutions for Env, at 61%, was higher (P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, characterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env, Because these clones were obtained from Indian seroconverters, they are likely to facilitate vaccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness.