Michler Katherine, Connell Bridgette J, Venter Willem D F, Stevens Wendy S, Capovilla Alexio, Papathanasopoulos Maria A
HIV Pathogenesis Research Laboratory, Department of Molecular Medicine and Haematology, University of the Witwatersrand Medical School, Parktown, Johannesburg, 2193, South Africa.
AIDS Res Hum Retroviruses. 2008 May;24(5):743-51. doi: 10.1089/aid.2007.0304.
CCR5 has preferentially been used by all circulating HIV-1 subtype C viruses for cell entry. Recently, we reported the highest proportion of CXCR4-utilizing primary isolates among a cohort of 20 South African AIDS patients. This study describes and compares the Env genotypic characteristics from these 20 HIV-1 subtype C (and unique CD recombinant) primary isolates. Fourteen primary isolates utilized CCR5, four (including the CD recombinant) used CXCR4, and two were dual tropic. Extensive analysis and comparison of important structural motifs such as the N-linked glycosylation sites, signal sequences, CD4-binding sites, variable loops, cleavage sites, known neutralizing antibody and small molecule inhibitor binding sites confirmed that other than the expected differences in the V3 loop, no sequence motifs distinguished between R5 and X4 tropism. Further correlation of the env genotype to functionally relevant motifs is necessary to elucidate the relationship between biologically and immunologically relevant sites and aid vaccine and novel drug design.
所有循环的HIV-1 C亚型病毒均优先利用CCR5进入细胞。最近，我们报告了在一组20名南非艾滋病患者中，利用CXCR4的原代分离株比例最高。本研究描述并比较了这20株HIV-1 C亚型（以及独特的CD重组型）原代分离株的Env基因特征。14株原代分离株利用CCR5，4株（包括CD重组型）利用CXCR4，2株为双嗜性。对重要结构基序进行广泛分析和比较，如N-连接糖基化位点、信号序列、CD4结合位点、可变环、裂解位点、已知中和抗体和小分子抑制剂结合位点，证实除了V3环存在预期差异外，R5和X4嗜性之间没有序列基序差异。Env基因型与功能相关基序的进一步关联对于阐明生物学和免疫学相关位点之间的关系以及辅助疫苗和新药设计是必要的。
