Characterisation of the Hepatitis C Virus Genotype 3 Glycoproteins

Hepatitis C virus (HCV) can be classified into six genotypes (1-6) which show 30% nucleotide sequence variability throughout the genome. HCV genotypes 1, 2 and 3 have a world-wide distribution but their prevalence differs from one geographical area to another. In Scotland there is an approximate 50/50 split between individuals infected with HCV genotype 1 and genotype 3. There is little evidence that disease progression or severity differs between the genotypes. On the other hand, one difference which has been consistently demonstrated is the better response of patients infected with genotypes 2 and 3 to interferon treatment than those infected with genotype 1. HCV encodes three structural proteins, core, E1 and E2. The two glycoproteins, E1 and E2, are bE1ieved to be the envE1ope proteins. The lack of a cE1l culture system for the production of HCV virions has meant that the proteins within the envE1ope of the HCV virion remain uncharacterised. However, recombinant forms of the E1 and E2 proteins have been shown to localise to the endoplasmic reticulum (ER) when expressed in cultured cE1ls and to interact with one another to form a complex (Ralston et al., 1993). E2 has also recently been shown to bind to the cE1l-surface molecule, CD81, which, as a result, has been proposed to be an HCV receptor (Pileri et al., 1998). These characteristics of the HCV glycoproteins have been described using constructs derived from genotype 1 only. Comparison of the properties of E1 and E2 with those of other genotypes would identify both conserved features, which are possibly essential to the virus life cycle, and genotype-specific features. In this study, the E1 and E2 proteins of genotype 3 were compared with those of genotype 1 with respect to antibody recognition, subcE1lular localisation, complex formation, glycosylation status and CD81-binding. The role of E2 in mediating resistance to interferon (IFN) through a proposed interaction with PKR (Taylor et al., 1999) was also inv