Alanine scanning of the hepatitis C virus core protein reveals numerous residues essential for production of infectious virus.
Hepatitis C virus (HCV) is an important human pathogen affecting an estimated 3% of the world's population. Recent advances have enabled in vitro propagation of the virus and allow assembly and egress to be investigated for the first time. As a component of the virion, the HCV core protein likely functions primarily in infectious virus production, although little is known about the determinants of this activity. To investigate the roles of core in the viral life cycle, we performed a comprehensive deletion and alanine scanning mutagenesis study of this protein in the context of a genotype 2a reporter virus. We have confirmed that core protein is essential for infectious virion production and have identified numerous residues required for this role. The infectivity of several assembly-defective core mutants could be rescued by compensatory mutations identified in p7 and NS2, suggesting genetic interactions with core and highlighting the importance of these nonstructural proteins in infectious virion morphogenesis.
Murray
Catherine L
CL
Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Ave., New York, NY 10021, USA.
Jones
Christopher T
CT
Tassello
Jodie
J
Rice
Charles M
CM
D000409:Alanine / Q000737:chemistry / Q000235:genetics; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002460:Cell Line; D016679:Genome, Viral / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D012694:Serine / Q000737:chemistry / Q000235:genetics; D014758:Viral Core Proteins / Q000235:genetics / Q000502:physiology*; D014771:Virion / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics*
D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D012694:Serine; D000409:Alanine