Nikolaitchik Olga, Keele Brandon, Gorelick Robert, Alvord W Gregory, Mazurov Dmitriy, Pathak Vinay K, Hu Wei-Shau
HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA.
AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Virology. 2015 Oct;484:334-340. doi: 10.1016/j.virol.2015.06.025. Epub 2015 Jul 9.
Recombination can assort polymorphic alleles to increase diversity in the HIV-1 population. To better understand the recombination potential of subtype A HIV-1, we generated viruses containing sequences from two variants circulating in Russia and analyzed the polymerase gene (pol) of the recombinants after one round of HIV-1 replication using single-genome sequencing. We observed that recombination occurred throughout pol and could easily assort alleles containing mutations that conferred resistance to currently approved antivirals. We measured the recombination rate in various regions of pol including a G-rich region that has been previously proposed to be a recombination hot spot. Our study does not support a recombination hot spot in this G-rich region. Importantly, of the 58 proviral sequences containing crossover event(s) in pol, we found that each sequence was a unique genotype indicating that recombination is a powerful genetic mechanism in assorting the genomes of subtype A HIV-1 variants.
重组可使多态性等位基因重新组合,从而增加HIV-1群体的多样性。为了更好地了解A型HIV-1的重组潜力,我们构建了含有俄罗斯流行的两种变体序列的病毒,并在一轮HIV-1复制后,使用单基因组测序分析重组体的聚合酶基因(pol)。我们观察到重组发生在整个pol基因中,并且能够轻松地将含有对目前批准的抗病毒药物产生抗性的突变的等位基因进行重新组合。我们测量了pol基因各个区域的重组率,包括一个先前被认为是重组热点的富含G的区域。我们的研究不支持该富含G的区域存在重组热点。重要的是,在pol基因中含有交叉事件的58个前病毒序列中,我们发现每个序列都是独特的基因型,这表明重组是一种强大的遗传机制,可对A型HIV-1变体的基因组进行重新组合。