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In vivo antiviral effects of mismatched double‐stranded RNA on duck hepatitis B virus
Author(s) -
Ijichi Katsushi,
Mitamura Keiji,
Ida Setsuko,
Machida Haruhiko,
Shimada Kaoru
Publication year - 1994
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.1890430212
Subject(s) - duck hepatitis b virus , virology , biology , in vivo , rna silencing , rna , virus , interferon , viral replication , hepatitis b virus , hepadnaviridae , rna interference , gene , biochemistry , microbiology and biotechnology
The antiviral activity and ability of mismatched double‐stranded RNA (m‐dsRNA), r(I) n′ r(C 12 ‐U) n′ to induce interferon (IFN) were evaluated in ducks chronically infected with duck hepatitis B virus (DHBV). When m‐dsRNA was administered intravenously at a single dose of 5 mg/kg, serum DHBV DNA concentrations decreased significantly for 3 days ( P < 0.002). However, the DHBV DNA concentrations returned to the pretreatment levels 4 days after treatment. Inhibition of DHBV DNA replication in the liver was also observed 2 days after treatment. Serum IFN activity peaked 3 hours after administration of m‐dsRNA, then rapidly declined. 2′‐5′ Oligo‐adenylate synthetase (2′‐5′ AS) activity increased gradually after treatment and remained elevated for at least 48 hours. In ducks receiving m‐dsRNA once daily for 7 consecutive days, serum DHBV DNA concentrations on the last day of treatment were decreased by 76 ± 12% ( P < 0.05) in ducks that received 0.2 mg of m‐dsRNA per kg and by 65 ± 12% ( P < 0.05) in ducks that received 1 mg of m‐dsRNA per kg. This decrease persisted for at least 2 weeks after the cessation of treatment in all ducks. These results suggest that m‐dsRNA effectively inhibits DHBV replication in vivo, and that IFN induction and stimulation of 2′–5′AS activity contribute to the inhibition of DHBV replication by m‐dsRNA. © 1994 Wiley‐Liss, Inc.