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A highly hydrophobic domain within hypervariable region 1 may be related to the entry of hepatitis C virus into cultured human hepatoma cells
Author(s) -
Kurihara Chie,
Tsuzuki Yoshikazu,
Hokari Ryota,
Nakashima Hiroyuki,
Mataki Norikazu,
Kuroki Masahiko,
Kawaguchi Atsushi,
Nagao Shigeaki,
Kondo Toshiro,
Miura Soichiro
Publication year - 2004
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.20213
Subject(s) - hypervariable region , virology , hepatitis a virus , virus , biology , hepatitis c virus , viral entry , antibody , viral replication , genetics
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. J. Med. Virol. 74:546–555, 2004. © 2004 Wiley‐Liss, Inc.