Antimicrobial Agents and Chemotherapy vol:58 pages:267-273
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.