Characterization of hypervariable region in hepatitis C virus envelope protein during acute and chronic infection.
Hepatitis C virus (HCV) causes persistent infection in most patients. To clarify the mechanisms underlying establishment of this persistent infection, nucleotide sequences of the E1/E2 region were characterized in 5 patients with acute and chronic HCV infection. We used direct DNA sequencing methods to identify the major sequence of HCV in each patient. Each HCV genome displayed a high frequency of nucleotide sequence variation in the hypervariable region (HVR) of E2. However, patient-specific conserved nucleotide sequences were identified in the E1/E2 region during the course of infection and conserved the higher-order protein structure. In the acute phase HCV infection, amino acid substitution in HVR-1 as the monthly rate of amino acids substitution per site (%) between each point exceeded 10.2%. In the chronic phase HCV infection, a significantly lower rate of amino acid substitution was observed in patients. The host immune responses to HVR-1 of each HCV isolates from all clinical courses were characterized using synthetic peptides and ELISA. One chronic patient serum (genotype 1b) did not react at all to its own HVR-1 peptides, however another patient (genotype 2b) reacted to all clinical course. These results indicated that HVR-1 might not always exhibit neutralizing epitopes of HCV infection. The sequence variation in HVR-1 may instead indicate the existence of various clones in acute phase infection and the adaption of these clones is thought to have caused persistent and chronic infection in each patient.
Higashi
K
K
Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Tsukiyama-Kohara
K
K
Tanaka
T
T
Tanaka
E
E
Kiyosawa
K
K
Kohara
M
M
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D002908:Chronic Disease; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics
C087035:E1 protein, Hepatitis C virus; C400562:HVR1 protein, Hepatitis C virus; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C091015:glycoprotein E2, Hepatitis C virus