Cevallos Cintia, Culasso Andrés C A, Modenutti Carlos, Gun Ana, Sued Omar, Avila María M, Flichman Diego, Delpino M Victoria, Quarleri Jorge
Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Heliyon. 2020 Dec 7;6(12):e05679. doi: 10.1016/j.heliyon.2020.e05679. eCollection 2020 Dec.
HIV-1 is characterized by its ability to mutate and recombine even at polymerase (pol) gene. However, pol-gene diversity is limited due to functional constraints. The aim of this study was to characterize longitudinally, by next-generation sequencing (NGS), HIV-1 variants based on pol-gene sequences, at intra- and inter-host level, from acute/early to chronic stages of infection, in the absence of antiretroviral therapy. Ten men who have sex with men (MSM) were recruited during primary infection and yearly followed for five years. Even after a maximum of a five-year follow-up period, the phylogenetic analysis of HIV-1 pol-gene sequences showed a host-defined structured pattern, with a predominance of purifying selection forces during the follow-up. MSM had been acutely infected by different HIV-1 variants mainly ascribed to pure subtype B, or BF recombinant variants and showed different genetic mosaicism patterns that last until the chronic stage, representing a major challenge for prevention strategies.
HIV-1的特点是即使在聚合酶(pol)基因处也有突变和重组的能力。然而,由于功能限制,pol基因的多样性是有限的。本研究的目的是在未接受抗逆转录病毒治疗的情况下,通过下一代测序(NGS),从感染的急性/早期到慢性阶段,在宿主内和宿主间水平上纵向表征基于pol基因序列的HIV-1变体。在初次感染期间招募了10名男男性行为者(MSM),并对其进行了为期五年的年度随访。即使在最长五年的随访期后,对HIV-1 pol基因序列的系统发育分析仍显示出宿主定义的结构化模式,随访期间纯化选择力占主导地位。MSM主要被不同的HIV-1变体急性感染,这些变体主要归因于纯B亚型或BF重组变体,并显示出持续到慢性阶段的不同遗传镶嵌模式,这对预防策略构成了重大挑战。