• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Scientific Publications by FDA Staff

  • Print
  • Share
  • E-mail

Search Publications



Starting Date

Ending Date

Order by

Entry Details

J Viral Hepat 2012 Dec;19(12):843-53

Distinct and overlapping genomic profiles and antiviral effects of Interferon-lambda and -alpha on HCV-infected and noninfected hepatoma cells.

Kohli A, Zhang X, Yang J, Russell RS, Donnelly RP, Sheikh F, Sherman A, Young H, Imamichi T, Lempicki RA, Masur H, Kottilil S


Summary. Recently, several SNPs in the region of the IL28B (IFN-lambda) gene have been associated with spontaneous clearance of hepatitis C virus (HCV) and enhanced cure rates for IFN-alfa-based therapies, suggesting a potential correlation between IFN-lambda and the ability to clear HCV. To understand the mechanism of IFN-lambda's as compared to IFN-alpha's antiviral activity, we performed a comprehensive analysis of their anti-HCV effects, whole genome transcriptome profiling with validation, and signalling of IFN-alpha and IFN-lambda using J6/JFH-1 and Huh7.5 cells in vitro. IFN-lambda and IFN-alpha exhibited comparable anti-HCV activity and gene expression profiles in Huh7.5 cells. While the majority of genes induced by IFN-alpha and IFN-lambda were similar, IFN-lambda exhibits profound, but delayed kinetics of IFN-stimulated genes (ISG) induction, while IFN-alpha induced more rapid induction of ISGs. Furthermore, the increased induction of ISG expression by IFN-lambda correlated with up-regulation of IFN-lambda receptor (IL-28RA) expression and more prolonged activation of the Jak-STAT signalling pathway. The findings from our comparative analysis of IFN-alpha and IFN-lambda in HCV-infected and noninfected cells support the clinical use of IFN-lambda as a potential alternative to IFN-alpha in the treatment of chronic hepatitis C.

Category: Journal Article
PubMed ID: #23121362 DOI: 10.1111/j.1365-2893.2012.01610.x
Includes FDA Authors from Scientific Area(s): Drugs
Entry Created: 2012-11-06 Entry Last Modified: 2012-12-06