Title: Ribavirin inhibits in vitro hepatitis E virus replication through depletion of cellular GTP pools and is moderately synergistic with alpha interferon
Authors: Debing, Yannick
Emerson, Suzanne U
Wang, Yijin
Pan, Qiuwei
Balzarini, Jan
Dallmeier, Kai
Neyts, Johan # ×
Issue Date: Jan-2014
Publisher: American Society for Microbiology (ASM)
Series Title: Antimicrobial Agents and Chemotherapy vol:58 pages:267-273
Abstract: Hepatitis E virus (HEV) is a common cause of acute hepatitis that results in high mortality in pregnant women and may establish chronic infections in immune-compromised patients. We demonstrate for the first time that interferon-α and ribavirin inhibit in vitro HEV replication, both in a subgenomic replicon and an infectious culture system based on a genotype 3 strain. Interferon-α showed a moderate but significant synergism with ribavirin. These findings corroborate the reported clinical effectiveness of both drugs. In addition, the antiviral activity of ribavirin against wild-type genotype 1, 2 and 3 strains was confirmed by immunofluorescent staining. Furthermore, the in vitro activity of ribavirin depends on depletion of intracellular GTP pools, as is evident from the fact that (i) other GTP-depleting agents (EICAR and mycophenolic acid) inhibit viral replication, (ii) exogenously added guanosine reverses the antiviral effects and (iii) a strong correlation (R(2) = 0.9998) exists between the antiviral activity and GTP depletion of ribavirin and other GTP-depleting agents.
ISSN: 0066-4804
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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