Ashokkumar Manickam, Nesakumar Manohar, Cheedarla Narayaniah, Vidyavijayan K K, Babu Hemalatha, Tripathy Srikanth P, Hanna Luke Elizabeth
Department of HIV/AIDS, National Institute for Research in Tuberculosis (ICMR) , Chennai, Tamil Nadu, India .
AIDS Res Hum Retroviruses. 2017 Aug;33(8):796-806. doi: 10.1089/AID.2016.0260. Epub 2017 Jun 19.
Mother-to-child transmission (MTCT) of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. Such studies would throw light on the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV. Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years). Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. Surprisingly, frequency of PNGS in the V5 region was found to revert rapidly, in about 75% of the sequences, which could surmise a fitness disadvantage in the variant forms. Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT.
艾滋病毒的母婴传播（MTCT）为研究病毒在已部分适应的宿主环境中早期病毒进化的动态变化提供了一个很好的机会。此类研究将揭示感染病毒的独特特征，这随后将有助于设计针对新感染和不断演变的艾滋病毒毒株的预防或治疗措施。因此，我们开展了一项研究，以确定感染艾滋病毒的婴儿（<2岁）前病毒包膜序列的遗传差异。详细分析揭示了潜在的N-糖基化位点（PNGS）的独特特征及其出现频率，这些特征基于包膜序列V1V2区域长度的差异。令人惊讶的是，在约75%的序列中，发现V5区域中PNGS的频率迅速恢复，这可能推测变异形式存在适应性劣势。此外，在V2和V3区域观察到稳定的净电荷，这促使我们分别推测传播变异体与整合素α4β7受体和R5共受体之间已确立的相互作用。简而言之，我们的观察结果表明，在我们人群中最近感染个体所获得病毒的包膜中，可变区长度的差异以及PNGS频率的变化可能是负责艾滋病毒在母婴传播感染早期传播的独特准种的重要特征。
