BACKGROUND & AIMS: Persistent infection with hepatitis C virus (HCV) leads to chronic hepatitis and hepatocellular carcinoma (HCC). RNA interference (RNAi) may act as a host antiviral response against viral RNA. METHODS: The effects of RNAi on both the replicative intermediates and the internal ribosome entry site (IRES) of HCV were studied by using HCV-related short interfering RNA (siRNA) detection assay. The mechanism that permits HCV to escape RNAi was studied by using RNAi assay materials. RESULTS: These studies demonstrate that the Dicer, an RNase enzyme that generates short siRNA, can target and digest both the IRES and the replicative intermediate of HCV into siRNA of approximately 22 nucleotides. Further studies also show that Dicer can inhibit the replication of the HCV subgenomic replicon. However, the HCV core protein inhibits this RNAi and rescues the replication of the HCV subgenomic replicon through a direct interaction with Dicer. CONCLUSIONS: RNAi is a limiting factor for HCV infection, and the core protein suppresses the RNA silencing-based antiviral response. This ability of the core protein to counteract the host defense may lead to a persistent viral infection and may contribute to the pathogenesis of HCV.
BACKGROUND & AIMS: Persistent infection with hepatitis C virus (HCV) leads to chronic hepatitis and hepatocellular carcinoma (HCC). RNA interference (RNAi) may act as a host antiviral response against viral RNA. METHODS: The effects of RNAi on both the replicative intermediates and the internal ribosome entry site (IRES) of HCV were studied by using HCV-related short interfering RNA (siRNA) detection assay. The mechanism that permits HCV to escape RNAi was studied by using RNAi assay materials. RESULTS: These studies demonstrate that the Dicer, an RNase enzyme that generates short siRNA, can target and digest both the IRES and the replicative intermediate of HCV into siRNA of approximately 22 nucleotides. Further studies also show that Dicer can inhibit the replication of the HCV subgenomic replicon. However, the HCV core protein inhibits this RNAi and rescues the replication of the HCV subgenomic replicon through a direct interaction with Dicer. CONCLUSIONS: RNAi is a limiting factor for HCV infection, and the core protein suppresses the RNA silencing-based antiviral response. This ability of the core protein to counteract the host defense may lead to a persistent viral infection and may contribute to the pathogenesis of HCV.
Authors: Qiuwei Pan; Scot D Henry; Herold J Metselaar; Bob Scholte; Jaap Kwekkeboom; Hugo W Tilanus; Harry L A Janssen; Luc J W van der Laan Journal: J Mol Med (Berl) Date: 2009-04-30 Impact factor: 4.599
Authors: Poornima Parameswaran; Ella Sklan; Courtney Wilkins; Trever Burgon; Melanie A Samuel; Rui Lu; K Mark Ansel; Vigo Heissmeyer; Shirit Einav; William Jackson; Tammy Doukas; Suman Paranjape; Charlotta Polacek; Flavia Barreto dos Santos; Roxana Jalili; Farbod Babrzadeh; Baback Gharizadeh; Dirk Grimm; Mark Kay; Satoshi Koike; Peter Sarnow; Mostafa Ronaghi; Shou-Wei Ding; Eva Harris; Marie Chow; Michael S Diamond; Karla Kirkegaard; Jeffrey S Glenn; Andrew Z Fire Journal: PLoS Pathog Date: 2010-02-12 Impact factor: 6.823
Authors: Oscar Aparicio; Elena Carnero; Xabier Abad; Nerea Razquin; Elizabeth Guruceaga; Victor Segura; Puri Fortes Journal: Nucleic Acids Res Date: 2009-11-19 Impact factor: 16.971