TY - JOUR
T1 - Activation of the interferon-β promoter during hepatitis C virus RNA replication
AU - Fredericksen, Brenda
AU - Akkaraju, Giridhar R.
AU - Foy, Eileen
AU - Wang, Chunfu
AU - Pflugheber, Jill
AU - Chen, Zhijian J.
AU - Gale, Michael
PY - 2002
Y1 - 2002
N2 - In this study we examined the impact of hepatitis C virus (HCV) RNA replication on the innate antiviral response of the host cell. Replication of an HCV subgenomic replicon stimulated the activation of the interferon (IFN)-β promoter and the production of IFN in human hepatoma cells. Using a variety of functional assays, we found that HCV RNA replication induced the activation and DNA-binding activity of NFκB and interferon regulatory factor (IRF)-1. In addition, microscopy experiments revealed a higher frequency of cells containing the nuclear-localized, active form of IRF-3 in HCV replicon cultures versus control cultures. Consistent with these observations, cells harboring the HCV replicon exhibited high basal level expression of a subset of IFN-stimulated antiviral genes. Our results indicate that HCV RNA replication can stimulate cellular antiviral programs that contribute to the assembly and activation of the IFN-β enhanceosome complex and initiation of the antiviral state. Stable HCV RNA replication in the face of the host antiviral response suggests that HCV may encode one or more proteins capable of overcoming specific antiviral processes, thereby supporting persistent infection.
AB - In this study we examined the impact of hepatitis C virus (HCV) RNA replication on the innate antiviral response of the host cell. Replication of an HCV subgenomic replicon stimulated the activation of the interferon (IFN)-β promoter and the production of IFN in human hepatoma cells. Using a variety of functional assays, we found that HCV RNA replication induced the activation and DNA-binding activity of NFκB and interferon regulatory factor (IRF)-1. In addition, microscopy experiments revealed a higher frequency of cells containing the nuclear-localized, active form of IRF-3 in HCV replicon cultures versus control cultures. Consistent with these observations, cells harboring the HCV replicon exhibited high basal level expression of a subset of IFN-stimulated antiviral genes. Our results indicate that HCV RNA replication can stimulate cellular antiviral programs that contribute to the assembly and activation of the IFN-β enhanceosome complex and initiation of the antiviral state. Stable HCV RNA replication in the face of the host antiviral response suggests that HCV may encode one or more proteins capable of overcoming specific antiviral processes, thereby supporting persistent infection.
UR - http://www.scopus.com/inward/record.url?scp=0036209661&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036209661&partnerID=8YFLogxK
U2 - 10.1089/088282402317340215
DO - 10.1089/088282402317340215
M3 - Article
C2 - 11952144
AN - SCOPUS:0036209661
SN - 0882-8245
VL - 15
SP - 29
EP - 40
JO - Viral Immunology
JF - Viral Immunology
IS - 1
ER -