In vivo antiviral effects of mismatched double-stranded RNA on duck hepatitis B virus.
The antiviral activity and ability of mismatched double-stranded RNA (m-dsRNA), r(I)n.r(C12-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.
Ijichi
K
K
Department of Infectious Diseases, University of Tokyo, Japan.
Mitamura
K
K
Ida
S
S
Machida
H
H
Shimada
K
K
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000097:blood / Q000187:drug effects; D004334:Drug Administration Schedule; D004372:Ducks; D018347:Hepadnaviridae Infections / Q000097:blood / Q000628:therapy*; D015611:Hepatitis B Virus, Duck / Q000187:drug effects / Q000502:physiology*; D007275:Injections, Intravenous; D016898:Interferon-alpha / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000382:microbiology; D011070:Poly I-C / Q000008:administration & dosage*; D011072:Poly U / Q000008:administration & dosage*; D012330:RNA, Double-Stranded / Q000008:administration & dosage*; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004279:DNA, Viral; D016898:Interferon-alpha; D012330:RNA, Double-Stranded; D011072:Poly U; C047490:poly(I).poly(c12,U); D011070:Poly I-C