Abstract

Response to interferon of patients infected with HCV has been variable. Recent studies suggested a region, termed IFN sensitivity determining region (ISDR) in the HCV NS5A gene, that are associated with resistance to interferon. The NS5A has also been shown to be a phosphoprotein, probably playing an important role in viral replication and viral-host interaction. Because of the functional importance of NS5A, our laboratory is conducting experiments to characterize its functions and identify cellular factors that are the functional targets of this HCV gene product. Using the yeast two hybrid system, several cellular gene products that interact specifically with NS5A have been identified. Experiments are under way to address the functional significance of these interactions. Effort is also being initiated to evaluate the clinical significance of sequence variations in NS5A. Detailed characterization of this virus-cell interaction and correlation to clinical disease may contribute to our understanding of HCV replication and mechanisms of hepatocellular injury.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK054505-01
Application #
6162033
Study Section
Special Emphasis Panel (DDB)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
National Institute of Diabetes and Digestive and Kidney Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Carpentier, Arnaud; Nimgaonkar, Ila; Chu, Virginia et al. (2016) Hepatic differentiation of human pluripotent stem cells in miniaturized format suitable for high-throughput screen. Stem Cell Res 16:640-50
Carpentier, Arnaud; Tesfaye, Abeba; Chu, Virginia et al. (2014) Engrafted human stem cell-derived hepatocytes establish an infectious HCV murine model. J Clin Invest 124:4953-64
Barth, Heidi; Rybczynska, Jolanta; Patient, Romuald et al. (2011) Both innate and adaptive immunity mediate protective immunity against hepatitis C virus infection in chimpanzees. Hepatology 54:1135-48
Rotman, Yaron; Liang, T Jake (2009) Coinfection with hepatitis C virus and human immunodeficiency virus: virological, immunological, and clinical outcomes. J Virol 83:7366-74
Su, Xiaowen; Yee, Leland J; Im, KyungAh et al. (2008) Association of single nucleotide polymorphisms in interferon signaling pathway genes and interferon-stimulated genes with the response to interferon therapy for chronic hepatitis C. J Hepatol 49:184-91
Modi, A A; Liang, T J (2008) Hepatitis C: a clinical review. Oral Dis 14:10-4
Huang, Ying; Feld, Jordan J; Sapp, Ronda K et al. (2007) Defective hepatic response to interferon and activation of suppressor of cytokine signaling 3 in chronic hepatitis C. Gastroenterology 132:733-44
Feld, Jordan J; Nanda, Santosh; Huang, Ying et al. (2007) Hepatic gene expression during treatment with peginterferon and ribavirin: Identifying molecular pathways for treatment response. Hepatology 46:1548-63
Kato, Takanobu; Matsumura, Takuya; Heller, Theo et al. (2007) Production of infectious hepatitis C virus of various genotypes in cell cultures. J Virol 81:4405-11
Lutchman, Glen; Danehower, Susan; Song, Byung-Cheol et al. (2007) Mutation rate of the hepatitis C virus NS5B in patients undergoing treatment with ribavirin monotherapy. Gastroenterology 132:1757-66

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