Microbiology Department, National Reference Center for AIDS Research, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
J Med Virol. 2012 Apr;84(4):570-81. doi: 10.1002/jmv.23243.
The human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same transmission routes which lead to high coinfection rates. Among HIV-infected individuals such rates reached 21% in Argentina, being HCV-1a the most predominant subtype. In this work, 25 HCV subtype 1a (HCV-1a) strains from Argentinean patients coinfected with HIV were studied based on E2 and NS5A sequences. Phylogenetic analyses indicated that 12 strains were highly related to each other, constituting a highly supported (posterior probability = 0.95) monophyletic group that we called "M." The remaining HCV strains (group dispersed or "D") were interspersed along the phylogenetic trees. When comparing both groups of HCV-1a, 10 amino acid differences were located in functional domains of E2 and NS5A proteins that appeared to affect eventually the peptides binding to MHC-I molecules thus favoring immune escape and contributing to the divergence of HCV genotypes. Bayesian coalescent analyses for HCV-1a cluster M isolates indicated that the time to the most recent common ancestor (tMRCA) overlaps with the age estimated recently for the HIV-BF epidemic in Argentina. Furthermore, the genomic characterization based on pol gene analysis from HIV viremic patients showed that most HIV isolates from patients coinfected with HCV-1a cluster M were BF recombinants with identical recombination patterns. In conclusion, these results suggest the presence of an HCV-1a monophyletic cluster with a potential HIV co-transmission by phylogenetic analyses.
人类免疫缺陷病毒 (HIV) 和丙型肝炎病毒 (HCV) 具有相同的传播途径,导致两者的合并感染率很高。在感染 HIV 的人群中,这种合并感染率在阿根廷达到了 21%,其中 HCV-1a 是最主要的亚型。在这项工作中,我们研究了来自阿根廷合并感染 HIV 的 HCV-1a 患者的 25 株 HCV 亚型 1a (HCV-1a) 株,基于 E2 和 NS5A 序列。系统进化分析表明,有 12 株 HCV-1a 株彼此高度相关,构成了一个高度支持的(后验概率=0.95)单系群,我们称之为“M”。其余 HCV 株(分散群或“D”)则散布在系统进化树中。当比较这两组 HCV-1a 时,发现 E2 和 NS5A 蛋白的功能域中存在 10 个氨基酸差异,这些差异似乎最终影响了与 MHC-I 分子结合的肽,从而有利于免疫逃逸,并导致 HCV 基因型的分化。对 HCV-1a 聚类 M 株的贝叶斯合并分析表明,最近共同祖先 (tMRCA) 的时间与最近估计的阿根廷 HIV-BF 流行的时间重叠。此外,对来自 HIV 病毒血症患者的 pol 基因分析进行的基因组特征分析表明,来自 HCV-1a 聚类 M 合并感染患者的大多数 HIV 分离株是 BF 重组体,具有相同的重组模式。总之,这些结果表明存在一个 HCV-1a 单系群,通过系统进化分析存在潜在的 HIV 共同传播。