HOMOTYPIC INTERACTION AND MULTIMERIZATION OF HEPATITIS-C VIRUS CORE PROTEIN

Hepatitis C virus (HCV) core protein constitutes a viral nucleocapsid and may possess multiple functions. In this study, we demonstrated the homotypic interaction and multimerization of HCV core protein in vitr o and in vivo. By using a yeast two-hybrid system, we showed that the amino-terminal hydrophilic portion (amino acids 1-115) of the core pro tein could interact with itself. Deletion analysis mapped the interact ing domain within amino acid residues 36-91. The homotypic interaction of the core protein was also confirmed by in vitro protein-protein bl otting assay using the recombinant HCV core proteins and by its bindin g to the glutathione S-transferase core fusion protein. The biological significance of the core protein self-interactions was demonstrated b y the detection of multimeric forms of the core protein in mammalian c ells. The domain responsible for multimerization was determined to be within the amino-terminal hydrophilic region (amino acids 1-115). Both the membrane-bound and the free core proteins exist in dimeric and mu ltimeric forms, suggesting that multimerization of the HCV core protei n occurred af an early stage of viral assembly and that the multimer f orms may be involved in multiple functions of the core protein. (C) 19 96 Academic Press. Inc.