Hepatitis C virus (HCV) diversity in HIV-HCV-coinfected subjects initiating highly active antiretroviral therapy
Hepatitis C virus (HCV) diversity in HIV-HCV-coinfected subjects initiating highly active antiretroviral therapy
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DOI：
10.1086/382959
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发表时间：
2004-04-15
影响因子：
6.4
通讯作者：
Chung, RT
中科院分区：
文献类型：
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作者：
Blackard, JT;Yang, YJ;Chung, RT
由于同时感染人类免疫缺陷病毒（HIV）和丙型肝炎病毒（HCV）的受试者死亡率增加，治疗反应率降低，了解HCV进化背后的选择压力对于制定控制这两种病毒的策略非常重要。因此，我们研究了11名开始高效抗逆转录病毒治疗（HAART）的hiv -HCV共感染受试者的HCV多样性。确定了不同类型的HCV对HIV抑制的病毒学反应。在48周的时间内，对几个基因组区域的准物种多样性进行了表征。共识数据表明，在HAART开始后，除5'非翻译区（UTR）外，所有基因座的病毒种群都发生了变化。个体内遗传距离和熵在高变区(HVR)-1最高。相反，5' UTR的变异是有限的。检测到针对HVR-1的阳性免疫选择压力，而不是其他蛋白质编码区域。这些数据表明，在HIV-HCV共感染者中，抑制HIV复制和重建免疫系统影响HCV多样性的机制有多种。
Because of increased mortality and reduced treatment response rates in subjects coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), understanding the selection pressures underlying the evolution of HCV is important for the development of strategies to control both viruses. We therefore investigated diversity of HCV in 11 HIV-HCV-coinfected subjects initiating highly active antiretroviral therapy ( HAART). Distinct categories of HCV virologic response to suppression of HIV were identified. The diversity of quasi species at several genomic regions was characterized over the course of a 48-week period. Consensus data suggested a shift in the virus population at all loci except the 5' untranslated region (UTR) after initiation of HAART. Intrasubject genetic distance and entropy were highest in hypervariable region (HVR)-1. In contrast, variation in the 5' UTR was limited. Positive immune selection pressure directed against HVR-1, but not other protein-coding regions, was also detected. These data suggest that there are several mechanisms by which suppression of HIV replication and a reconstituted immune system influence diversity of HCV in HIV-HCV coinfected subjects.