INVESTIGATION OF THE PATTERN OF HEPATITIS-C VIRUS SEQUENCE DIVERSITY IN DIFFERENT GEOGRAPHICAL REGIONS - IMPLICATIONS FOR VIRUS CLASSIFICATION

Genotypes of hepatitis C virus (HCV) present within 104 samples from H CV-infected individuals from Africa, the Middle East, the Indian subco ntinent and South-East Asia were identified by sequence comparisons in the core and NS-5 regions. Relatively short sequences (such as the 22 2 bp fragment of NS-5) provided effective discrimination of types, sub types and isolates, and produced equivalent relationships between geno types as were found upon comparison of longer sequences of NS-5, of th e core region, and by comparison of the limited number of complete gen omic sequences currently available. Measurement of evolutionary distan ces in the core and NS-5 regions allowed 79 of the 104 samples to be i dentified as examples of known genotypes, while 17 of the remainder co uld be provisionally classified as new subtypes of types 1 (Nigeria), 2 (Gambia), 3 (India, Pakistan and Bangladesh) and 4 (Middle East) on the basis of sequence comparison in core and NS-5 (n = 9) or provision ally using core alone (n = 8). The remaining sequences from Thailand m ade up two groups showing no close similarity to any of the six major genotypes classified to date, although one corresponded to an as yet u nclassified variant of HCV also found in Thailand. However, phylogenet ic analysis of the core and NS-5 regions indicated a distant relations hip between these sequences with variants found in Vietnam and with ty pe 6a, and collectively they formed a diverse single phylogenetic grou p. The existence of great diversity within a single genotype was also found amongst type 3 sequences in the Indian subcontinent, amongst typ e 4 variants in Central Africa and the Middle East, and amongst type v ariants in Nigeria. These findings may provide clues for understanding the origins and mechanisms of transmission of HCV.