THE ENTIRE NUCLEOTIDE-SEQUENCE AND CLASSIFICATION OF A HEPATITIS-C VIRUS ISOLATE OF A NOVEL GENOTYPE FROM AN INDONESIAN PATIENT WITH CHRONIC LIVER-DISEASE

Three hepatitis C virus (HCV) isolates were obtained from patients wit h chronic liver diseases in Indonesia which were not classifiable into any of the genotypes I/1a, II/1b, III/2a, IV/2b or V/3a reported prev iously. The entire nucleotide sequence was determined for one HCV isol ate (HC-G9); the remaining two isolates were of the same genotype base d on a > 95% similarity within their partial sequences spanning 2927 n ucleotides (nt). The HC-G9 genome consisted of 9440 nt including the 5 ' untranslated region of 341 nt, an open reading frame of 9033 nt codi ng for a polyprotein of 3011 amino acids and the 3' untranslated regio n of 66 nt (U stretch of 17 to 47 nt at the extreme 3' terminus exclud ed). It differed by 20 to 33% in nucleotide sequence from any of 14 HC V genomes of genotypes I/1a to IV/2b whose full-length sequences are k nown. By the unweighted pair-group method with arithmetic mean, HC-G9 was on a major branch (group 1) of the phylogenetic tree of HCV to whi ch genotypes I/1a and II/1b belong. It is proposed, therefore, that th e novel genotype for HC-G9 should be called 1c. A method was developed to identify genotype 1c by PCR with a primer deduced from the core ge ne that was specific to it. Since genotype 1c was detected in seven (1 5%) of 48 HCV RNA samples from Indonesian patients with chronic liver disease, but not in any of 1097 from other districts of the world, it appears to have evolved and remained in Indonesia. In addition to its epidemiological importance, the association of genotype 1c HCV with th e severity of liver disease and its response to interferons deserve to be evaluated.