Sequence heterogeneity within the 5'-terminal region of the hepatitis GB 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, However, unlike hepatitis C virus, an open reading frame possessing a complete core protein was not identified in the original isolate, Methods: To verify the sequence at the 5'-end of the GB virus C genome, we amplified approximately 600 nucleotides from this region from 35 globally distributed individuals, The nucleotide sequences were translated in all possible reading frames and then examined for conserved motifs indicative of nucleocapsid or core-like peptides, Results: Forty-two unique GB virus C sequences were obtained from the 35 individuals, The deduced amino acid sequences upstream of the putative Fl gene from each isolate 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 held in common among all isolates, although it was located very near the 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 differs 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 emphasizes the importance of investigating the correlation between infecting subtype and the severity of liver disease and/or responsiveness to treatment of GB virus C-associated hepatitis.