Effective inhibition of hepatitis E virus replication in A549 cells and piglets by RNA interference (RNAi) targeting RNA-dependent RNA polymerase

• Published in: Antiviral research 2009-09, Vol.83 (3), p.274-281
• Main Authors: Huang, Fen, Hua, Xiuguo, Yang, Shixing, Yuan, Congli, Zhang, Wen
• Format: Article
• Language: English
• Subjects: A549 cells; Alanine Transaminase - blood; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Aspartate Aminotransferases - blood; Biological and medical sciences; Cell Line; Hepatitis E - drug therapy; Hepatitis E - virology; Hepatitis E virus; Hepatitis E virus - drug effects; Human viral diseases; Infectious diseases; Kidney - virology; Medical sciences; Pharmacology. Drug treatments; Piglets; RNA Interference; RNA, Small Interfering - genetics; RNA, Small Interfering - pharmacology; RNA, Small Interfering - therapeutic use; RNA-dependant RNA polymerase; Swine; Treatment Outcome; Viral diseases; Viral hepatitis; Virus Replication - drug effects
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2009.06.008

RNA interference (RNAi) is a natural mechanism for suppressing or silencing expression of aberrant or foreign genes. It is a powerful antiviral strategy that has been widely employed to protect hosts from viral infection. Hepatitis E (HE) is an acute fulminant hepatitis in adults that has particularly high mortality in pregnant women. At this point in time, there is no vaccine or antiviral treatment that is effective against the infectious agent, HEV. The nonstructural polyprotein region possesses an RNA-dependent RNA polymerase (RdRp) that is responsible for the replication of the viral RNA genome. RdRp is therefore regarded as one of the most attractive candidates for RNA interference (RNAi). In the present study, the high efficiency and specificity of siRNA were evaluated by Real-Time quantitative PCR and Western blot assays. Protective effects against HEV infection were achieved in A549 cells and in piglets. In piglets treated with a shRNA-RdRp-1 expression plasmid prior to HEV inoculation, HEV antigens were significantly reduced in the liver, spleen, and kidneys, and the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were clearly decreased. These results suggested that RNAi is a potentially effective antiviral strategy against HEV replication and infection.