Antiviral Actions of Interferons

doi:10.1128/CMR.14.4.778-809.2001

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Clinical Microbiology Reviews, October 2001, p. 778-809, Vol. 14, No. 4
0893-8512/01/$04.00+0 DOI: 10.1128/CMR.14.4.778-809.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Antiviral Actions of Interferons

Charles E. Samuel^*

Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California 93106-9610

Tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), aswell as strategies evolved by viruses to antagonize the actionsof IFNs. Furthermore, advances made while elucidating the IFNsystem have contributed significantly to our understanding inmultiple areas of virology and molecular cell biology, rangingfrom pathways of signal transduction to the biochemical mechanismsof transcriptional and translational control to the molecularbasis of viral pathogenesis. IFNs are approved therapeutics andhave moved from the basic research laboratory to the clinic. Amongthe IFN-induced proteins important in the antiviral actions ofIFNs are the RNA-dependent protein kinase (PKR), the 2',5'-oligoadenylatesynthetase (OAS) and RNase L, and the Mx protein GTPases. Double-strandedRNA plays a central role in modulating protein phosphorylationand RNA degradation catalyzed by the IFN-inducible PKR kinaseand the 2'-5'-oligoadenylate-dependent RNase L, respectively,and also in RNA editing by the IFN-inducible RNA-specific adenosinedeaminase (ADAR1). IFN also induces a form of inducible nitricoxide synthase (iNOS2) and the major histocompatibility complexclass I and II proteins, all of which play important roles inimmune response to infections. Several additional genes whoseexpression profiles are altered in response to IFN treatment andvirus infection have been identified by microarray analyses. Theavailability of cDNA and genomic clones for many of the componentsof the IFN system, including IFN- $alpha$ , IFN- $beta$ , and IFN- $gamma$ , their receptors,Jak and Stat and IRF signal transduction components, and proteinssuch as PKR, 2',5'-OAS, Mx, and ADAR, whose expression is regulatedby IFNs, has permitted the generation of mutant proteins, cellsthat overexpress different forms of the proteins, and animalsin which their expression has been disrupted by targeted genedisruption. The use of these IFN system reagents, both in cellculture and in whole animals, continues to provide important contributionsto our understanding of the virus-host interaction and cellularantiviralresponse.

^* Mailing address: Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA93106-9610. Phone: (805) 893-3097. Fax: (805) 893-5780. E-mail:samuel{at}lifesci.lscf.ucsb.edu.

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Nanda, S. K., Baron, M. D. (2006). Rinderpest Virus Blocks Type I and Type II Interferon Action: Role of Structural and Nonstructural Proteins.. J. Virol. 80: 7555-7568 [Abstract] [Full Text]
Baccam, P., Beauchemin, C., Macken, C. A., Hayden, F. G., Perelson, A. S. (2006). Kinetics of influenza a virus infection in humans.. J. Virol. 80: 7590-7599 [Abstract] [Full Text]
Chen, K., Huang, J., Zhang, C., Huang, S., Nunnari, G., Wang, F.-x., Tong, X., Gao, L., Nikisher, K., Zhang, H. (2006). Alpha Interferon Potently Enhances the Anti-Human Immunodeficiency Virus Type 1 Activity of APOBEC3G in Resting Primary CD4 T Cells.. J. Virol. 80: 7645-7657 [Abstract] [Full Text]
Alvarez, V. A., Ridenour, D. A., Sabatini, B. L. (2006). Retraction of synapses and dendritic spines induced by off-target effects of RNA interference.. J. Neurosci. 26: 7820-7825 [Abstract] [Full Text]
Schweizer, M., Matzener, P., Pfaffen, G., Stalder, H., Peterhans, E. (2006). "Self" and "Nonself" Manipulation of Interferon Defense during Persistent Infection: Bovine Viral Diarrhea Virus Resists Alpha/Beta Interferon without Blocking Antiviral Activity against Unrelated Viruses Replicating in Its Host Cells. J. Virol. 80: 6926-6935 [Abstract] [Full Text]
Vaha-Koskela, M. J.V., Kallio, J. P., Jansson, L. C., Heikkila, J. E., Zakhartchenko, V. A., Kallajoki, M. A., Kahari, V.-M., Hinkkanen, A. E. (2006). Oncolytic capacity of attenuated replicative semliki forest virus in human melanoma xenografts in severe combined immunodeficient mice.. Cancer Res. 66: 7185-7194 [Abstract] [Full Text]
Guerra, S., Lopez-Fernandez, L. A., Garcia, M. A., Zaballos, A., Esteban, M. (2006). Human Gene Profiling in Response to the Active Protein Kinase, Interferon-induced Serine/threonine Protein Kinase (PKR), in Infected Cells: INVOLVEMENT OF THE TRANSCRIPTION FACTOR ATF-3 IN PKR-INDUCED APOPTOSIS. J. Biol. Chem. 281: 18734-18745 [Abstract] [Full Text]
Brukman, A., Enquist, L. W. (2006). Suppression of the interferon-mediated innate immune response by pseudorabies virus.. J. Virol. 80: 6345-6356 [Abstract] [Full Text]
Cardenas, W. B., Loo, Y.-M., Gale, M. Jr., Hartman, A. L., Kimberlin, C. R., Martinez-Sobrido, L., Saphire, E. O., Basler, C. F. (2006). Ebola Virus VP35 Protein Binds Double-Stranded RNA and Inhibits Alpha/Beta Interferon Production Induced by RIG-I Signaling.. J. Virol. 80: 5168-5178 [Abstract] [Full Text]
Lin, R.-J., Chang, B.-L., Yu, H.-P., Liao, C.-L., Lin, Y.-L. (2006). Blocking of Interferon-Induced Jak-Stat Signaling by Japanese Encephalitis Virus NS5 through a Protein Tyrosine Phosphatase-Mediated Mechanism.. J. Virol. 80: 5908-5918 [Abstract] [Full Text]
Garcia-Sastre, A., Biron, C. A. (2006). Type 1 interferons and the virus-host relationship: a lesson in detente .. Science 312: 879-882 [Abstract] [Full Text]
Battcock, S. M., Collier, T. W., Zu, D., Hirasawa, K. (2006). Negative Regulation of the Alpha Interferon-Induced Antiviral Response by the Ras/Raf/MEK Pathway. J. Virol. 80: 4422-4430 [Abstract] [Full Text]
Peng, T., Kotla, S., Bumgarner, R. E., Gustin, K. E. (2006). Human rhinovirus attenuates the type I interferon response by disrupting activation of interferon regulatory factor 3.. J. Virol. 80: 5021-5031 [Abstract] [Full Text]
Weber, F., Wagner, V., Rasmussen, S. B., Hartmann, R., Paludan, S. R. (2006). Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses.. J. Virol. 80: 5059-5064 [Abstract] [Full Text]
Nusinzon, I., Horvath, C. M. (2006). Positive and Negative Regulation of the Innate Antiviral Response and Beta Interferon Gene Expression by Deacetylation. Mol. Cell. Biol. 26: 3106-3113 [Abstract] [Full Text]

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