Gordon M, De Oliveira T, Bishop K, Coovadia H M, Madurai L, Engelbrecht S, Janse van Rensburg E, Mosam A, Smith A, Cassol S
HIV-1 Molecular Virology and Bioinformatics Laboratories, Africa Centre for Health and Population Studies and the Nelson R. Mandela School of Medicine, University of Natal, Congella 4013, Durban, South Africa.
J Virol. 2003 Feb;77(4):2587-99. doi: 10.1128/jvi.77.4.2587-2599.2003.
The KwaZulu-Natal region of South Africa is experiencing an explosive outbreak of human immunodeficiency virus type 1 (HIV-1) subtype C infections. Understanding the genetic diversity of C viruses and the biological consequences of this diversity is important for the design of effective control strategies. We analyzed the protease gene, the first 935 nucleotides of reverse transcriptase, and the C2V5 envelope region of a representative set of 72 treatment-naïve patients from KwaZulu-Natal and correlated the results with amino acid signature and resistance patterns. Phylogenetic analysis revealed multiple clusters or "lineages" of HIV-1 subtype C that segregated with other C viruses from southern Africa. The same pattern was observed for both black and Indian subgroups and for retrospective specimens collected prior to 1990, indicating that multiple sublineages of HIV-1 C have been present in KwaZulu-Natal since the early stages of the epidemic. With the exception of three nonnucleoside reverse transcriptase inhibitor mutations, no primary resistance mutations were identified. Numerous accessory polymorphisms were present in the protease, but none were located at drug-binding or active sites of the enzyme. One frequent polymorphism, I93L, was located near the protease/reverse transcriptase cleavage site. In the envelope, disruption of the glycosylation motif at the beginning of V3 was associated with the presence of an extra protein kinase C phosphorylation site at codon 11. Many polymorphisms were embedded within cytotoxic T lymphocyte or overlapping cytotoxic T-lymphocyte/T-helper epitopes, as defined for subtype B. This work forms a baseline for future studies aimed at understanding the impact of genetic diversity on vaccine efficacy and on natural susceptibility to antiretroviral drugs.
南非夸祖鲁 - 纳塔尔地区正在经历1型人类免疫缺陷病毒（HIV - 1）C亚型感染的爆发式流行。了解C型病毒的基因多样性及其多样性所带来的生物学后果对于设计有效的控制策略至关重要。我们分析了夸祖鲁 - 纳塔尔地区72名未经治疗患者的一组代表性样本的蛋白酶基因、逆转录酶的前935个核苷酸以及C2V5包膜区域，并将结果与氨基酸特征和耐药模式进行了关联。系统发育分析揭示了HIV - 1 C亚型的多个簇或“谱系”，它们与来自南部非洲的其他C型病毒分离。在黑人和印度亚组以及1990年之前收集的回顾性样本中都观察到了相同的模式，这表明自疫情早期以来，HIV - 1 C的多个亚谱系就已存在于夸祖鲁 - 纳塔尔地区。除了三个非核苷类逆转录酶抑制剂突变外，未发现主要耐药突变。蛋白酶中存在许多辅助多态性，但没有一个位于该酶的药物结合或活性位点。一种常见的多态性I93L位于蛋白酶/逆转录酶切割位点附近。在包膜中，V3起始处糖基化基序的破坏与密码子11处额外的蛋白激酶C磷酸化位点的存在有关。许多多态性嵌入了细胞毒性T淋巴细胞或重叠的细胞毒性T淋巴细胞/T辅助表位内，如针对B亚型所定义那样。这项工作为未来旨在了解基因多样性对疫苗效力和对抗逆转录病毒药物自然易感性影响的研究奠定了基础。
