Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins.
Based on the flavi- and pestivirus model of genome organization for the hepatitis C virus (HCV) (1-5), the nucleotide and deduced amino acid sequences of the putative envelope (E1) and the junction between the E1 and NS1/envelope 2 (E2) region from six different human isolates of HCV were compared with the nucleotide and predicted amino acid sequences of the prototype hepatitis C virus (HCV-1) (5). The overall percentage of nucleotide and amino acid changes among all six isolates, including HCV-1, from nucleotide 713 to 1630 (amino acid 129 to 437) was between 3 and 7%, which is comparable to that seen in some flaviviruses (6-8). An analysis of the number of nucleotide and deduced amino acid sequence changes among all six isolates and HCV-1 revealed a moderately variable domain of approximately 40 amino acids in the E1 region and a hypervariable domain (Region V) of approximately 28 amino acids, which is directly downstream from a putative signal peptide sequence, in the junction between E1 and NS1/E2. A similar hypervariable domain is not found in the C-terminus of the envelope polypeptide or in the N-terminus of the NS1 polypeptide domain of the flaviviruses. These findings suggest that the mature NS1/E2 polypeptide starts about amino acid 380 and that the NS1/E2 domain may correspond to a second envelope glycoprotein as in the case of the pestivirus. The observed heterogeneity in the putative structural proteins of HCV may have important ramifications for future vaccine development.
Weiner
A J
AJ
Chiron Corporation, Emeryville, California 94608.
Brauer
M J
MJ
Rosenblatt
J
J
Richman
K H
KH
Tung
J
J
Crawford
K
K
Bonino
F
F
Saracco
G
G
Choo
Q L
QL
Houghton
M
M
D000595:Amino Acid Sequence; D001483:Base Sequence; D002213:Capsid / Q000235:genetics*; D005416:Flavivirus / Q000235:genetics*; D005814:Genes, Viral; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010576:Pestivirus / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics; D014758:Viral Core Proteins / Q000235:genetics*; D014759:Viral Envelope Proteins / Q000235:genetics*; D017361:Viral Nonstructural Proteins
D015345:Oligonucleotide Probes; D014157:Transcription Factors; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins