Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy.
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Viruses. 2023 Jul 20;15(7):1580. doi: 10.3390/v15071580.
A common feature of the mammalian (family ) is an RNA genome that contains an extremely high frequency of adenine (31.7-38.2%) while being extremely poor in cytosine (13.9-21.2%). Such a biased nucleotide composition has implications for codon usage, causing a striking difference between the frequency of synonymous codons in and that in their hosts. To test whether primate present differences in codon and amino acid composition, we assembled a dataset of genome sequences that includes SIV species infecting Old-World monkeys and African apes, HIV-2, and the four groups of HIV-1. Using principal component analysis, we found that HIV-1 shows a significant enrichment in adenine plus thymine in the third synonymous codon position and in adenine and guanine in the first and second nonsynonymous codon positions. Similarly, we observed an enrichment in adenine and in guanine in nonsynonymous first and second codon positions, which affects the amino acid composition of the proteins Gag, Pol, Vif, Vpr, Tat, Rev, Env, and Nef. This result suggests an effect of natural selection in shaping codon usage. Under the hypothesis that the use of synonyms in HIV-1 could reflect adaptation to that of genes expressed in specific cell types, we found a highly significant correlation between codon usage in HIV-1 and monocytes, which was remarkably higher than that with B and T lymphocytes. This finding is in line with the notion that monocytes represent an HIV-1 reservoir in infected patients, and it could help understand how this reservoir is established and maintained.
哺乳动物反转录病毒科的一个共同特征是其 RNA 基因组含有极高频率的腺嘌呤(31.7-38.2%),同时胞嘧啶含量极低(13.9-21.2%)。这种偏向性的核苷酸组成对密码子的使用有影响,导致反转录病毒科和其宿主之间同义密码子的频率存在显著差异。为了检验灵长类反转录病毒是否在密码子和氨基酸组成上存在差异,我们收集了一组包括感染旧世界猴和非洲猿的 SIV 物种、HIV-2 以及 HIV-1 的四个组的基因组序列。通过主成分分析,我们发现 HIV-1 在第三同义密码子位置的腺嘌呤加胸腺嘧啶以及第一和第二非同义密码子位置的腺嘌呤和鸟嘌呤中存在显著富集。同样,我们观察到第一和第二非同义密码子位置的腺嘌呤和鸟嘌呤富集,这影响了 Gag、Pol、Vif、Vpr、Tat、Rev、Env 和 Nef 蛋白的氨基酸组成。这一结果表明自然选择在塑造密码子使用方面发挥了作用。根据 HIV-1 中使用同义词可能反映了对特定细胞类型中表达的基因的适应的假设,我们发现 HIV-1 中的密码子使用与单核细胞高度相关,这与 B 和 T 淋巴细胞的相关性显著更高。这一发现与单核细胞是感染患者中 HIV-1 储存库的观点一致,并且可以帮助理解这个储存库是如何建立和维持的。