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Tandem Repeats of Lactoferrin‐Derived Anti‐Hepatitis C Virus Peptide Enhance Antiviral Activity in Cultured Human Hepatocytes
Author(s) -
Abe Kenichi,
Nozaki Akito,
Tamura Kazushi,
Ikeda Masanori,
Naka Kazuhito,
Dansako Hiromichi,
Hoshino Hiroo,
Tanaka Katsuaki,
Kato Nobuyuki
Publication year - 2007
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2007.tb03882.x
Subject(s) - lactoferrin , biology , hepatitis c virus , western blot , microbiology and biotechnology , virology , amino acid , gene , hepatocyte , virus , in vitro , biochemistry
Previously, we found that bovine and human lactoferrin (LF) specifically inhibited hepatitis C virus (HCV) infection in cultured non‐neoplastic human hepatocyte‐derived PH5CH8 cells, and we identified 33 amino acid residues (termed C‐s3–33; amino acid 600–632) from human LF that were primarily responsible for the binding activity to the HCV E2 envelope protein and for the inhibiting activity against HCV infection. Since the anti‐HCV activity of C‐s3–33 was weaker than that of human LF, we speculated that an increase of E2 protein‐binding activity might contribute to the enhancement of anti‐HCV activity. To test this possibility, we made two repeats [(C‐s3–33) 2 ] and three repeats [(C‐s3–33) 3 ] of C‐s3–33 and characterized them. Far‐Western blot analysis revealed that the E2 protein‐binding activities of (C‐s3–33) 2 and (C‐s3–33) 3 became stronger than that of the C‐s3–33, and that the binding activity of (C‐s3–33) 3 was stronger than that of (C‐s3–33) 2 . Using an HCV infection system in PH5CH8 cells, we demonstrated that the anti‐HCV activities of (C‐s3–33) 2 and (C‐s3–33) 3 became stronger than that of the C‐s3–33. Furthermore, using a recently developed infection system with a VSV pseudotype harboring the green fluorescent protein gene and the native E1 and E2 genes, we demonstrated that the antiviral activities of (C‐s3–33) 2 and (C‐s3–33) 3 were stronger than that of C‐s3–33. These results suggest that tandem repeats of LF‐derived anti‐HCV peptide are useful as anti‐HCV reagents.