Comparative molecular biology of flaviviruses and hepatitis C virus

Currently available sequence information suggests that the genome organization of hepatitis C virus is similar to that of flaviviruses. A positive-stranded genomic RNA contains a single long open reading frame (ORF) which is flanked by 5' and 3' noncoding sequences. This RNA codes for structural proteins at the 5' end (starting with the capsid protein) and a set of nonstructural proteins in the remainder of the genome. The latter provide essential virus-specific functions for the viral life cycle, such as protease, helicase, and RNA replicase activities. The sequence motifs characteristic of the corresponding functional protein domains are separated by similar spacings in the nonstructural regions of hepatitis C virus and flaviviruses. The structural region of the hepatitis C virus appears to consist of a capsid protein which is larger than that of flaviviruses and two putative envelope proteins which are presumably different in molecular weight and much more heavily glycosylated than their counterparts in flaviviruses. A study group of the International Committee on the Taxonomy of viruses proposes to include hepatitis C virus as a genus into the family 'flaviviridae'.