Defective Hepatic Response to Interferon and Activation of Suppressor of Cytokine Signaling 3 in Chronic Hepatitis C

Ying Huang, Jordan J. Feld, Ronda K. Sapp, Santosh Nanda, Jiing Huey Lin, Lawrence M. Blatt, Michael W. Fried, Krishna Murthy, T. Jake Liang

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Background & Aims: Approximately half of hepatitis C virus (HCV)-infected patients do not respond to current interferon (IFN)-α combination therapy. To understand IFN-α resistance in vivo, we examined the dynamic responses to both type I and type II IFNs, human IFN (hIFN)-α, -γ, and consensus IFN, in the chimpanzee model. Methods: Naive and HCV-infected chimpanzees were treated with 3 forms of hIFNs in vivo. Quantitative real-time polymerase chain reaction was performed to evaluate the expression of IFN-stimulated genes (ISGs) in both peripheral blood mononuclear cells and liver to compare the responses to hIFN between naive and infected chimpanzees. The hepatic expression of IFN signaling components and inhibitory regulators including suppressor of cytokine signaling 3 (SOCS3) were assessed. SOCS3 expression was also evaluated in the liver of HCV-infected patients undergoing IFN treatment. Results: The in vivo responses to all 3 hIFNs were much lower in the HCV-infected chimpanzees than those in the naive chimpanzees. This defect was particularly evident in the liver because induction of hepatic ISGs was barely detectable in the infected animals. Following IFN administration, the expression of SOCS3 was significantly up-regulated, possibly through induction of interleukin-6, in the liver of HCV-infected chimpanzees. HCV-infected humans also showed a differential pattern of hepatic SOCS3 expression in response to IFN that is associated with treatment response. Conclusions: Our data indicate a predominantly defective hepatic response to IFN in HCV-infected chimpanzees, which is probably mediated through the activation of SOCS3 and may explain the nonresponse of many HCV patients to IFN-based therapy.

Original languageEnglish (US)
Pages (from-to)733-744
Number of pages12
Issue number2
StatePublished - Feb 2007
Externally publishedYes

ASJC Scopus subject areas

  • Gastroenterology


Dive into the research topics of 'Defective Hepatic Response to Interferon and Activation of Suppressor of Cytokine Signaling 3 in Chronic Hepatitis C'. Together they form a unique fingerprint.

Cite this