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Semin Liver Dis 2011; 31(4): 356-374
DOI: 10.1055/s-0031-1297925
© Thieme Medical Publishers

New Insights into the HCV Quasispecies and Compartmentalization

Patrizia Farci1
  • 1Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
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Publication Date:
21 December 2011 (online)

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ABSTRACT

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.

KEYWORDS

Hepatitis C virus - quasispecies - compartmentalism - immune escape - viral persistence

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Patrizia Farci

National Institutes of Health, 50 South Drive, MSC 8009

Building 50, Room 6529, Bethesda, MD 20892

Email: pfarci@niaid.nih.gov