SEQUENCE HETEROGENEITY WITHIN THE 5'-TERMINAL REGION OF THE HEPATITISGB VIRUS-C GENOME AND EVIDENCE FOR GENOTYPES

associated with hepatitis in humans, GB virus C bears some resemblance to hepatitis C virus in its genomic sequence and organization, Howeve r, unlike hepatitis C virus, an open reading frame possessing a comple te core protein was not identified in the original isolate, Methods: T o verify the sequence at the 5'-end of the GB virus C genome, we ampli fied approximately 600 nucleotides from this region from 35 globally d istributed individuals, The nucleotide sequences were translated in al l possible reading frames and then examined for conserved motifs indic ative of nucleocapsid or core-like peptides, Results: Forty-two unique GB virus C sequences were obtained from the 35 individuals, The deduc ed amino acid sequences upstream of the putative Fl gene from each iso late varied in length and composition, such that a conserved core-like sequence was not apparent; No core-like sequences were evident in the other reading frames, There was, however, a single methionine codon h eld in common among all isolates, although it was located very near th e presumed amino-terminus of the putative Fl protein, Further analysis of the sequences for their evolutionary relatedness demonstrated the existence of five GB virus C subtypes that demonstrated a significant correlation with geographic distribution, Conclusions: GB virus C diff ers from hepatitis C virus and GB virus B in that it does not encode a nucleocapsid or core protein, The existence of GB virus C subtypes em phasizes the importance of investigating the correlation between infec ting subtype and the severity of liver disease and/or responsiveness t o treatment of GB virus C-associated hepatitis.