The molecular genetics and diversity of the Hepatitis C virus genome

A number of different genotypes of the Hepatitis C virus have been reported in New Zealand (Cooper et al. 1993, Woodfield et al. 1994). However little is known about the distribution of genotypes, the extent of strain diversity within genotypes or whether genotype correlates with severity of disease. In this study hepatitis C virus RNA was investigated using reverse transcription polymerase chain reaction with primers targeting the 5' UT and NS-5 regions. Genotypes were identified by restriction endonuclease cleavage with enzymes MboI, HaeIII and BstNI, single stranded conformational polymorphism analysis and confirmed by direct cycle sequencing. Clinical details and hepatic activity index score were recorded and aligned with genotype. Genotypes 1, 2, 3, 4 were detected, along with subtypes 1a, 1b, 2a, 2b, 3a, 4a and variants of 1a, 1b and 3a. Subtypes 2a and 4a have not been reported previously in New Zealand. Dominant subtypes 1b-variant and 3a comprised more than 50% of cases in the 224 patients studied. Patients with subtype 1a tended to have a lower mean HAI score than those with other types. In conclusion the extent of strain diversity in New Zealand is greater than previously reported, most major recognised genotypes are found in New Zealand and subtypes 1b, 2b, 3a, 4a and a 1b-variant may be associated with a more severe outcome of infection