No abstract

The line probe assay can be used in patients with chronic HCV infection in the United States. In patients with chronic hepatitis C referred to tertiary centers in the United States, type 1 is the most common HCV genotype. Disease activity and viremia levels do not differ among patients chronically infected with HCV types 1, 2, or 3.

Serum samples from 139 US patients with chronic hepatitis C virus (HCV) infection were studied using six different genotyping systems, including both molecular and serologic methods, to determine the applicability of these approaches and the prevalence of various HCV subtypes. The concordance of genotyping results based on the various systems (except for core polymerase chain reaction genotyping) was good (93.5%). Subtypes 1a and 1b were prevalent (37.4%). Subtypes 2a (2.2%), 2b (8.6%), and 3a (5.8%) were less common. HCV genotypes could not be determined in 3.4%-16.5% of samples depending on the method used. HCV type 2 was associated with greater histologic activity but lower serum HCV RNA levels (P < .05), whereas type 3 was associated with lower serum alanine aminotransferase levels (P < .05). These data demonstrate a high concordance between HCV genotyping systems and provide a foundation for comparison of genotyping data between studies using different systems. HCV types 1a and 1b are both prevalent in the United States.

Comparison of 33 epidemiologically distinct GBV-C/hepatitis G virus complete genome sequences suggests the existence of four major phylogenetic groupings that are equally divergent from the chimpanzee isolate GBV-C tro and have distinct geographical distributions. These four groupings are not consistently reproduced by analysis of the virus 5'-noncoding region (5'-NCR), or of individual genes or subgenomic fragments with the exception of the E2 gene as a whole or of 200-600 nucleotide fragments from its 3' half. This region is upstream of a proposed anti-sense reading frame and contains conserved potential RNA secondary structures that may be capable of directing the internal initiation of translation. Phylogenetic analysis of this region from certain South African isolates is consistent with previous analysis of the 5'-NCR suggesting that these belong to a fifth group. The geographical distribution of virus variants is consistent with a long evolutionary history that may parallel that of pre-historic human migrations, implying that the long-term evolution of this RNA virus is extremely slow.

The 5' end of the NS-4 protein of different genotypes of hepatitis C virus (HCV) is highly variable in nucleotide and inferred amino acid sequence, with frequent predicted amino acid substitutions between all six of the major HCV genotypes described to date. This region has been shown to be antigenic by epitope mapping, and elicits antibody in HCV-infected individuals with a detectable type-specific component. We have used this sequence data to specify branched peptides for an indirect binding/competition assay to detect typespecific antibody to each major genotype. A total of 183 out of 210 samples (87%) from blood donors and patients with chronic hepatitis C infected with genotypes 1 to 6 showed detectable type-specific antibody to NS-4 peptides that in almost all cases (> 97 %) corresponded to the genotype detected by a PCR typing method. These findings demonstrate the existence of major antigenic differences between genotypes of HCV, and indicate how infection with different variants of HCV may be detected by a serological test.