Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Semin Liver Dis. 2011 Nov;31(4):356-74. doi: 10.1055/s-0031-1297925. Epub 2011 Dec 21.
Hepatitis C virus (HCV) is a hepatotropic RNA virus with an extraordinary propensity to persist in the vast majority of infected individuals. During replication, because of the inherent infidelity of the viral RNA polymerase, each progeny RNA genome contains mutations that lead to a continuous diversification of the viral population. Consequently, HCV circulates in vivo as a quasispecies, which is a dynamic distribution of divergent but closely related genomes subjected to a continuous process of genetic variation, competition, and selection. This genomic heterogeneity confers a remarkable advantage to the viral population allowing for a rapid adaptation to a changing environment when the virus is subject to selective constraints exerted by the host, such as antiviral immunity, or external to the host, such as antiviral therapy. The large reservoir of variants provided by the quasispecies represents a great challenge for the control of HCV infection and has important biologic implications for viral persistence, host cell tropism, antiviral drug resistance, and development of an HCV vaccine. This review discusses the molecular mechanisms of HCV genetic variation and the biologic and clinical relevance of the quasispecies nature of HCV.
丙型肝炎病毒 (HCV) 是一种嗜肝 RNA 病毒，绝大多数感染者都有持续存在的倾向。在复制过程中，由于病毒 RNA 聚合酶的固有不准确性，每个子代 RNA 基因组都包含导致病毒群体持续多样化的突变。因此，HCV 在体内作为准种循环，这是一种受遗传变异、竞争和选择的连续过程影响的、具有不同但密切相关的基因组的动态分布。这种基因组异质性赋予了病毒群体显著的优势，使其能够在病毒受到宿主施加的选择性限制（如抗病毒免疫）或宿主外部的选择性限制（如抗病毒治疗）时，迅速适应不断变化的环境。准种提供的大量变体库为控制 HCV 感染带来了巨大挑战，并且对病毒持续存在、宿主细胞嗜性、抗病毒药物耐药性和 HCV 疫苗的发展具有重要的生物学意义。这篇综述讨论了 HCV 遗传变异的分子机制以及 HCV 准种性质的生物学和临床相关性。
