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Content Provider | World Health Organization (WHO)-Global Index Medicus |
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Author | Mu, Xinmeng Jasmine Pagliaccetti, Nicole E. Eduardo, Roger Bandi, Prasanthi Kleinstein, Steven H. Robek, Michael D. |
Description | Author Affiliation: Pagliaccetti NE ( Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.) |
Abstract | The interferon (IFN)-related cytokine interleukin (IL)-29 (also known as IFN-lambda1) inhibits virus replication by inducing a cellular antiviral response similar to that activated by IFN-alpha/beta. However, because it binds to a unique receptor, this cytokine may function cooperatively with IFN-alpha/beta or IFN-gamma during natural infections to inhibit virus replication, and might also be useful therapeutically in combination with other cytokines to treat chronic viral infections such as hepatitis C (HCV). We therefore investigated the ability of IL-29 and IFN-alpha or IFN-gamma to cooperatively inhibit virus replication and induce antiviral gene expression. Compared with the individual cytokines alone, the combination of IL-29 with IFN-alpha or IFN-gamma was more effective at blocking vesicular stomatitis virus and HCV replication, and this cooperative antiviral activity correlated with the magnitude of induced antiviral gene expression. Although the combined effects of IL-29 and IFN-alpha were primarily additive, the IL-29/IFN-gamma combination synergistically induced multiple genes and had the greatest antiviral activity. Two different mechanisms contributed to the enhanced gene expression induced by the cytokine combinations: increased activation of ISRE promoter elements and simultaneous activation of both ISRE and GAS elements within the same promoter. These findings provide new insight into the coregulation of a critical innate immune response by functionally distinct cytokine families. |
ISSN | 00219258 |
e-ISSN | 1083351X |
Journal | Journal of Biological Chemistry |
Issue Number | 44 |
Volume Number | 283 |
Language | English |
Publisher | American Society for Biochemistry and Molecular Biology (United States) |
Publisher Date | 2008-10-31 |
Publisher Place | United States |
Access Restriction | Open |
Subject Keyword | Gene Expression Regulation Hepacivirus Metabolism Hepatitis C Interferons Interleukins Antiviral Agents Pharmacology Cell Line, Tumor Cell Proliferation Cell Survival Gene Expression Profiling Virology Models, Biological Molecular Sequence Data Promoter Regions, Genetic Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
Content Type | Text |
Resource Type | Article |
Subject | Molecular Biology Cell Biology Biochemistry |
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