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Deep Profiling Identifies Selection of Nonsynonymous Amino Acid Substitutions in HIV-1 Envelope During Early Infection.
AIDS Research and Human Retroviruses ( IF 1.5 ) Pub Date : 2020-11-25 , DOI: 10.1089/aid.2020.0143
Manickam Ashokkumar 1 , Sathyamurthi Pattabiraman 1 , Srikanth P Tripathy 1 , Ujjwal Neogi 2 , Luke Elizabeth Hanna 1
Affiliation  

Understanding the evolutionary dynamics of the viruses within an individual at or near the moment of transmission can provide critical inputs for the design of an effective vaccine for HIV infection. In this study, high-throughput sequencing technology was employed to analyze the evolutionary rate in viruses obtained at a single time point from drug-naive recently infected infants and adults in the chronic stage of disease. Gene-wise nonsynonymous (pN) and synonymous (pS) mutation rates were estimated and compared between the two groups. Significant differences were observed in the evolutionary rates between viruses in the early and late stages of infection. Higher rates of adaptive mutations in the HIV-1 envelope gene (env) were found in the chronic viruses as compared with those in the early stages of HIV infection. Conversely, percentage of nonsynonymous substitutions in env was found to be higher in recently transmitted viruses. In addition, a positive correlation was found between mutation and the evolutionary rate, and infectivity titer in recent infection. Despite the small sample size, the study identified useful information about viral evolution on transmission-associated bottlenecks. The effect of intraindividual HIV-1 evolution at the population level was highly contemporary, and the higher percentage of nonsynonymous substitutions seen in env during recent HIV-1 infection has suggested a pattern of convergent evolution leading to a positive selection for survival fitness and disease progression.

中文翻译:

深度分析确定早期感染期间 HIV-1 包膜中非同义氨基酸替代物的选择。

了解病毒在传播时或传播时附近的个体内部病毒的进化动态可以为设计有效的 HIV 感染疫苗提供关键输入。在这项研究中,高通量测序技术被用来分析在单个时间点从新近感染的处于慢性疾病阶段的婴儿和成人中获得的病毒的进化率。估计和比较两组之间的基因非同义 (pN) 和同义 (pS) 突变率。在感染的早期和晚期阶段,病毒之间的进化速率存在显着差异。HIV-1 包膜基因(env) 与 HIV 感染早期阶段的病毒相比,在慢性病毒中被发现。相反,在最近传播的病毒中发现env中非同义替换的百分比更高。此外,在最近的感染中发现突变与进化率和传染性滴度之间存在正相关。尽管样本量很小,但该研究确定了有关传播相关瓶颈的病毒进化的有用信息。个体内 HIV-1 进化在人群水平上的影响是高度现代的,并且在env 中看到的非同义替换百分比更高 在最近的 HIV-1 感染期间,表明了一种趋同进化模式,导致对生存适应性和疾病进展的积极选择。
更新日期:2020-12-03
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