Africa Health Research Institute, Durban, South Africa.
Africa Health Research Institute, Durban, South Africa; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
Virology. 2023 Jun;583:14-26. doi: 10.1016/j.virol.2023.04.001. Epub 2023 Apr 10.
The genetic diversity of HIV impedes vaccine development. Identifying the viral properties of transmitted/founder (T/F) variants may provide a common vaccine target. To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. Eighteen full-length T/F clones were generated from 9 women and six chronic infection clones were from 2 individuals. All clones but one were non-recombinant subtype C. Three of the 5 T/F clones and 3 chronic clones tested replicated efficiently in PBMCs and utilised CCR5 coreceptor for cell entry. Transmitted/founder and chronic infection clones displayed heterogenous in vitro replicative capacity and resistance to type I interferon. T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. Our findings suggest MTF transmission may select viruses with compact envelopes.
HIV 的遗传多样性阻碍了疫苗的开发。鉴定传播/初始（T/F）变异体的病毒特性可能为通用疫苗靶点提供依据。为了研究 T/F 病毒的生物学性质，我们从异性恋男传女（MTF）传播的 Fiebig 阶段 I 急性 HIV-1 感染（AHI）期间检测到的女性以及感染一年后的女性中，使用基于 In-Fusion 的克隆技术构建了全长克隆。从 9 名女性中产生了 18 个全长 T/F 克隆，从 2 名个体中产生了 6 个慢性感染克隆。除 1 个克隆外，所有克隆均是非重组亚型 C。5 个 T/F 克隆和 3 个慢性克隆中的 3 个在 PBMC 中有效复制，并利用 CCR5 核心受体进入细胞。T/F 和慢性感染克隆在体外复制能力和对 I 型干扰素的耐药性方面存在差异。T/F 病毒的Env 糖蛋白较短，Env 中的 N 连接糖基化位点较少。我们的研究结果表明，MTF 传播可能会选择具有紧凑包膜的病毒。
