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Inhibitory effect of 2'-fluoro-5-methyl-beta-L-arabinofuranosyl-uracil on duck hepatitis B virus replication.

Publication ,  Journal Article
Aguesse-Germon, S; Liu, SH; Chevallier, M; Pichoud, C; Jamard, C; Borel, C; Chu, CK; Trépo, C; Cheng, YC; Zoulim, F
Published in: Antimicrob Agents Chemother
February 1998

The antiviral activity of 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil (L-FMAU), a novel L-nucleoside analog of thymidine known to be an inhibitor of hepatitis B virus (HBV) replication in hepatoma cells (2.2.1.5 cell line), was evaluated in the duck HBV (DHBV) model. Short-term oral administration (5 days) of L-FMAU (40 mg/kg of body weight/day) to experimentally infected ducklings induced a significant decrease in the level of viremia. This antiviral effect was sustained in animals when therapy was prolonged for 8 days. The histological study showed no evidence of liver toxicity in the L-FMAU-treated group. By contrast, microvesicular steatosis was found in the livers of dideoxycytidine-treated animals. L-FMAU administration in primary duck hepatocyte cultures infected with DHBV induced a dose-dependent inhibition of both virion release in culture supernatants and intracellular viral DNA synthesis, without clearance of viral covalently closed circular DNA. By using a cell-free system for the expression of an enzymatically active DHBV reverse transcriptase, it was shown that L-FMAU triphosphate exhibits an inhibitory effect on the incorporation of dAMP in the viral DNA primer. Thus, our data demonstrate that L-FMAU inhibits DHBV replication in vitro and in vivo. Long-term administration of L-FMAU for the eradication of viral infection in animal models of HBV infection should be evaluated.

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Published In

Antimicrob Agents Chemother

DOI

ISSN

0066-4804

Publication Date

February 1998

Volume

42

Issue

2

Start / End Page

369 / 376

Location

United States

Related Subject Headings

  • Virus Replication
  • Microbiology
  • Liver
  • Hepatitis B Virus, Duck
  • Hepadnaviridae Infections
  • Ducks
  • DNA, Viral
  • Arabinofuranosyluracil
  • Antiviral Agents
  • Animals
 

Citation

APA
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MLA
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Aguesse-Germon, S., Liu, S. H., Chevallier, M., Pichoud, C., Jamard, C., Borel, C., … Zoulim, F. (1998). Inhibitory effect of 2'-fluoro-5-methyl-beta-L-arabinofuranosyl-uracil on duck hepatitis B virus replication. Antimicrob Agents Chemother, 42(2), 369–376. https://doi.org/10.1128/AAC.42.2.369
Aguesse-Germon, S., S. H. Liu, M. Chevallier, C. Pichoud, C. Jamard, C. Borel, C. K. Chu, C. Trépo, Y. C. Cheng, and F. Zoulim. “Inhibitory effect of 2'-fluoro-5-methyl-beta-L-arabinofuranosyl-uracil on duck hepatitis B virus replication.Antimicrob Agents Chemother 42, no. 2 (February 1998): 369–76. https://doi.org/10.1128/AAC.42.2.369.
Aguesse-Germon S, Liu SH, Chevallier M, Pichoud C, Jamard C, Borel C, et al. Inhibitory effect of 2'-fluoro-5-methyl-beta-L-arabinofuranosyl-uracil on duck hepatitis B virus replication. Antimicrob Agents Chemother. 1998 Feb;42(2):369–76.
Aguesse-Germon, S., et al. “Inhibitory effect of 2'-fluoro-5-methyl-beta-L-arabinofuranosyl-uracil on duck hepatitis B virus replication.Antimicrob Agents Chemother, vol. 42, no. 2, Feb. 1998, pp. 369–76. Pubmed, doi:10.1128/AAC.42.2.369.
Aguesse-Germon S, Liu SH, Chevallier M, Pichoud C, Jamard C, Borel C, Chu CK, Trépo C, Cheng YC, Zoulim F. Inhibitory effect of 2'-fluoro-5-methyl-beta-L-arabinofuranosyl-uracil on duck hepatitis B virus replication. Antimicrob Agents Chemother. 1998 Feb;42(2):369–376.

Published In

Antimicrob Agents Chemother

DOI

ISSN

0066-4804

Publication Date

February 1998

Volume

42

Issue

2

Start / End Page

369 / 376

Location

United States

Related Subject Headings

  • Virus Replication
  • Microbiology
  • Liver
  • Hepatitis B Virus, Duck
  • Hepadnaviridae Infections
  • Ducks
  • DNA, Viral
  • Arabinofuranosyluracil
  • Antiviral Agents
  • Animals