Modulation of interferon signaling by hepatitis C virus non-structural 5A protein: implication of genotypic difference in interferon treatment.
Interferon (IFN) response rate in hepatitis C virus (HCV) patients has been varied with genotypes. In this study, we investigated the effects of HCV NS5A protein on IFN resistance and compared the genotypic differences of NS5A. We showed that IFN-α-, poly I:C-, and Sendai virus-induced ISRE transcriptional activities were inhibited by both genotype 1b and 2a NS5A protein. We demonstrated that not only genotype 1b but also genotype 2a NS5A exerted the similar extent of IFN-α-induced antiviral activity. We showed that NS5A derived from both genotype 1b and 2a showed no significant differential IFN responses as seen in HCV patients. These data imply that some other host factor may be involved in genotypic differences of IFN antagonism in HCV patients.
Kang
Sang-Min
SM
National Research Laboratory of Hepatitis C Virus, Ilsong Institute of Life Science, Hallym University, Dongan-gu, Anyang, Republic of Korea.
Won
Seung-Jae
SJ
Lee
Gun-Hee
GH
Lim
Yun-Sook
YS
Hwang
Soon B
SB
D021581:Active Transport, Cell Nucleus; D000998:Antiviral Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D024882:Drug Resistance, Viral / Q000235:genetics*; D020868:Gene Silencing; D016174:Hepacivirus / Q000235:genetics* / Q000378:metabolism; D006526:Hepatitis C / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D011070:Poly I-C / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000378:metabolism; D029082:Sendai virus; D014158:Transcription, Genetic / Q000187:drug effects; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D016898:Interferon-alpha; D016209:Interleukin-8; D011070:Poly I-C; D050794:STAT1 Transcription Factor; D017361:Viral Nonstructural Proteins; C494079:STAT1 protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase