A highly hydrophobic domain within hypervariable region 1 may be related to the entry of hepatitis C virus into cultured human hepatoma cells.
Interaction of the envelope glycoprotein of hepatitis C virus (HCV) with a cellular receptor(s) is thought to be essential for the initial steps of HCV infection. However, the mechanisms of HCV infection remain unclear. The aim of the present study was to determine the features of HCV that enable efficient entry of the virus into human hepatocytes. Variations of hypervariable region 1 (HVR1) sequences in HCV inocula and in infected human hepatoblastoma HepG2 cells were examined. Immunofluorescence of inoculated HepG2 cells with anti-HCV core antibodies demonstrated that HCV structural proteins were expressed in the cytoplasm, and their entry into HepG2 cells was confirmed. When the HVR1 amino acid sequences were compared, HVR1 quasispecies in the inoculated cells showed more uniformity than those of the inocula. Although there were no statistically significant differences between the two groups, hydrophobic residues were observed more frequently in the HVR1 amino acids from inoculated cells than in the HVR1 amino acids from the inocula. Results of hydropathy analysis revealed that highly hydrophobic domains exist in the middle of HVR1 in the inoculated cells in 7 of 10 patients. The results suggest that limited HCV populations are able to enter HepG2 cells and that the highly hydrophobic domain existing within the HVR1 may play an important role in the entry of HCV into cells.
Second Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Chie
C
Kurihara
Yoshikazu
Y
Tsuzuki
Ryota
R
Hokari
Hiroyuki
H
Nakashima
Norikazu
N
Mataki
Masahiko
M
Kuroki
Atsushi
A
Kawaguchi
Shigeaki
S
Nagao
Toshiro
T
Kondo
Soichiro
S
Miura
D000906:Antibodies; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000821:virology*; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000502:physiology*; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D014407:Tumor Cells, Cultured
D000906:Antibodies; D022801:Complementarity Determining Regions