Genetic heterogeneity and molecular epidemiology of GB virus C hepatitis Gvirus in China

Objective: The inter- and intrapatient genetic variation of GB virus C (GBV -C)/hepatitis G virus (HGV) was investigated to characterize the molecular epidemiologic profile of GBV-C/HGV infection in China, an area endemic for viral hepatitis. The intrapatient variation of hepatitis C virus (HCV) from the same patients was compared to that of GBV-C/HGV. Study Design/Methods: GB virus C/HGV RNA was amplified by polymerase chain reaction in 88 patients with hepatitis C, hepatitis B or presumed non-A-E h epatitis from three cities in China. Five clones of the GBV-C/HGV NS3 regio n were sequenced from each GBV-C/HGV RNA-positive patient. The correspondin g region of HCV was also sequenced from patients co-infected with HCV. Repr esentative sequences of the GBV-C/HGV NS3 region from each patient and thos e of isolates from other continents were subjected to phylogenetic analyses . Results: GB virus C/HGV was detected in 22 (25.25%) of 88 patients: 9 (21.4 %) of 42 patients with presumed non-A-E hepatitis, 10 (27.7%) of 36 patient s with hepatitis C, 3 (30.0%) in 10 patients with hepatitis B and C, and in none of 60 volunteer blood donors. The extent of nucleotide variation was less between Chinese isolates (2.4-17%; median, 10.4%) than between Chinese isolates and seven isolates from outside China (10.5-19.5%; median, 15.3%) . Intrapatient sequence variation ranged from 0 to 1.75%, with a mean of 0. 57 +/- 0.51%. Phylogenetic analysis grouped most Chinese isolates into four geographically specific clusters with a divergence of 10% to 16% from each other. The ratio of nonsynonymous to synonymous substitutions of GBV-C/HGV (Ka/Ks 0.019) was much lower than for HCV (0.071) in the same patients. Conclusion: Chinese isolates of GBV-C/HGV are genetically distinct. There a re local strains as well as shared strains between different locales. The e xtent of amino acid sequence conservation suggests strong selection against nonsynonymous substitutions in the GBV-C/HGV genome. (C) Lipponcott Willia ms & Wilkins, Inc.