Centro Nacional de Referencia para el SIDA, Departamento de Microbiologia, Universidad de Buenos Aires, Buenos Aires, Argentina.
J Med Virol. 2012 Apr;84(4):562-9. doi: 10.1002/jmv.23233.
HIV infection has a significant impact on the natural progression of liver disease caused by infection with hepatitis B virus (HBV), but its role in the molecular evolution of HBV is unknown. It is difficult to study the molecular evolution of HBV longitudinally considering its genomic complexity, which implies the analysis of paired samples. This study aimed to analyze the difference in the evolutionary dynamics of HBV among patients with HIV and uninfected individuals. In this study, 17 patients infected chronically with HBV were recruited, 9 of them were co-infected with HIV. Patients were HBe antigen-positive and infected with HBV genotype A. Paired plasma samples were collected from each patient 3 years apart, and they were compared subsequently to each other. The HBV phylogenetic inference among isolates from patients infected with HBV and co-infected with HBV and HIV tends to cluster separately. Likewise, when comparing the HBV evolutionary rate and genetic distances, values were higher in the former in both preC/C and S genomic regions. Intra-host analyses of HBV isolates revealed high diversity and complexity of quasispecies among patients infected with HBV exhibiting high numbers of viral variants and genetic distance. In summary, after studying the HBV molecular evolution among isolates ascribed to genotype A at inter- and intra-host levels, HBV exhibited low quasispecies complexity and diversity as well as low evolutionary rates in the presence of HIV co-infection, suggesting that the co-infection may have an impact on the HBV molecular evolution most likely from the weakened cellular immune response.
HIV 感染对乙型肝炎病毒（HBV）感染引起的肝病自然进程有重大影响，但 HIV 感染在 HBV 的分子进化中的作用尚不清楚。由于其基因组的复杂性，很难对 HBV 的分子进化进行纵向研究，这意味着需要对配对样本进行分析。本研究旨在分析 HIV 感染者和未感染者 HBV 分子进化的差异。本研究纳入了 17 例慢性 HBV 感染者，其中 9 例合并 HIV 感染。患者均为 HBe 抗原阳性，感染 HBV 基因型 A。每位患者均采集了相隔 3 年的配对血浆样本，随后对这些样本进行了比较。从 HBV 和 HIV 合并感染患者的分离株中进行 HBV 系统发育推断，其倾向于分别聚类。同样，当比较前 C/C 和 S 基因组区域的 HBV 进化率和遗传距离时，在前者中这两个值均更高。HBV 分离株的宿主内分析显示，高病毒变异体数量和遗传距离的 HBV 感染者的准种具有高度多样性和复杂性。总之，在对基因型 A 的 HBV 分离株进行宿主间和宿主内水平的分子进化研究后发现，在 HIV 合并感染的情况下，HBV 的准种复杂性和多样性较低，进化率也较低，提示合并感染可能主要通过削弱细胞免疫应答来影响 HBV 的分子进化。
