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Intracellular single‐chain antibody against hepatitis B virus core protein inhibits the replication of hepatitis B virus in cultured cells
Author(s) -
Yamamoto Masato,
Hayashi Norio,
Takehara Tetsuo,
Ueda Keiji,
Mita Eiji,
Tatsumi Tomohide,
Sasaki Yutaka,
Kasahara Akinori,
Hori Masatsugu
Publication year - 1999
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510300105
Subject(s) - hepatitis b virus , virology , hepatitis b virus pre beta , viral replication , biology , microbiology and biotechnology , intracellular , antibody , virus , hepatitis b virus dna polymerase , immunology
Hepatitis B virus (HBV) is one of the major causes of chronic liver diseases and hepatocellular carcinoma. In this study, we used a single chain antibody (sFv), which is a man‐made antibody with a strong affinity of immunoglobulin, to inhibit HBV replication. Because HBV replication can only take place in the viral nucleocapsid made of HBV core protein (HBc), we generated anti‐HBc sFv and examined whether intracellular anti‐HBc sFv could inhibit viral replication in the human hepatoblastoma‐derived cell line that produces HBV (HB611). With respect to HBV replication intermediates, both single‐stranded and partially double‐stranded DNA intermediates were markedly suppressed in the cells expressing anti‐HBc sFv, although HBV RNA intermediates were not affected. This suggested that intracellular anti‐HBc sFv inhibited HBV DNA replication by inhibiting reverse transcription from HBV pregenome RNA to single‐stranded DNA. Because the sFv‐HBc complex was detected in the cells expressing anti‐HBc sFv by immunoprecipitation analysis but the quantity of intracellular HBc was not affected, the anti‐HBc sFv was suggested to inhibit HBV DNA replication by interfering with the function of HBc. These results indicate that intracellular sFv against HBc might be effective as a novel active molecule for gene therapy of hepatitis B.