Nucleotide sequence and mutation rate of the H strain of hepatitis C virus.

Abstract

Patient H is an American patient who was infected with hepatitis C virus (HCV) in 1977. The patient became chronically infected and has remained so for the past 13 years. In this study, we compared the nucleotide and predicted amino acid sequences of the HCV genome obtained from plasma collected in 1977 with that collected in 1990. We find that the two HCV isolates differ at 123 of the 4923 (2.50%) nucleotides sequenced. We estimate that the mutation rate of the H strain of HCV is -1.92 x 10-3 base substitutions per genome site per year. The nucleotide changes were exclusively base substitutions and were unevenly distributed throughout the genome. A relatively high rate of change was observed in the region of the HCV genome that corresponds to the nonstructural protein 1 gene region of flaviviruses, where 44 of 960 (4.6%) nucleotides were different. Within this region there was a 39-nucleotide domain in which 28.2% of the nucleotides differed between the two isolates. In contrast, relatively few nucleotide substitutions were observed in the 5' noncoding region, where only 2 of 276 (0.7%) nucleotides were different. Our results suggest that the mutation rate of the HCV genome is similar to that of other RNA viruses and that genes appear to be evolving at different rates within the virus genome.

Molecular study of HCV detection, genotypes and their routes of transmission in North West Frontier Province, Pakistan

“…High genetic heterogeneity has been noted for HCV, with a nucleotide substitution rate of 1.44暳10 -3 -1.92暳10 -3 per site per year [22] . These mutations result in diversification and evolution of different HCV genotypes.…”

Codon optimization and mRNA amplification effectively enhances the immunogenicity of the hepatitis C virus nonstructural 3/4A gene

“…2 The genetic heterogeneity of HCV is a result of the high viral replication rate of 10 10 -10 13 viral particles daily 3 together with spontaneous nucleotide substitutions of 10 À2 -10 À3 substitutions per nucleotide per year. 4,5 This suggests that vaccine development should be targeted against genetically stable regions of the HCV genome. It has been shown that DNA immunizations can induce both specific antibodies and cell-mediated responses against the structural and nonstructural (NS) HCV proteins in mice.…”

Comparison of the rate of sequence variation in the hypervariable region of E2/NS1 region of hepatitis C virus in normal and hypogammaglobulinemic patients

“…In particular, a 27-amino acid region at the amino terminus of E2/NS1 has been shown to vary greatly between isolates and has become known as hypervariable region 1 (HVR). [1][2][3] The HVR appears to be structurally unconstrained and tolerates extensive amino acid variation; it probably encodes part of an envelope peptide that is exposed to the host' s immune response. 4 Studies have indicated the presence within this region of linear B-cell epitopes recognized by neutralizing antibody, and amino acid variation occurring during chronic infection has been put forward as the mechanism underlying the escape from antibody binding.…”