Journal article

Morbillivirus Control of the Interferon Response: Relevance of STAT2 and mda5 but Not STAT1 for Canine Distemper Virus Virulence in Ferrets

Nicholas Svitek, Ingo Gerhauser, Christophe Goncalves, Elena Grabski, Marius Doering, Ulrich Kalinke, Danielle E Anderson, Roberto Cattaneo, Veronika von Messling

Journal of Virology | AMER SOC MICROBIOLOGY | Published : 2014

Abstract

UNLABELLED: The V proteins of paramyxoviruses control the innate immune response. In particular, the V protein of the genus Morbillivirus interferes with the signal transducer and activator of transcription 1 (STAT1), STAT2, and melanoma differentiation-associated protein 5 (mda5) signaling pathways. To characterize the contributions of these pathways to canine distemper virus (CDV) pathogenesis, we took advantage of the knowledge about the mechanisms of interaction between the measles virus V protein with these key regulators of innate immunity. We generated recombinant CDVs with V proteins unable to properly interact with STAT1, STAT2, or mda5. A virus with combined STAT2 and mda5 deficien..

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Awarded by CIHR


Awarded by NIH


Awarded by German Research Foundation (DFG)


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

The p125-Luc plasmid was a kind gift of Georg Kochs at the Institute for Medical Microbiology and Hygiene, University of Freiburg, Germany, and the mda5 and RIG-I expression plasmids were generously provided by Manoj Krishnan at the Duke-NUS Graduate Medical School. We thank all laboratory members for continuing support and lively discussions.This work was supported by CIHR grant MOP66989, funding from the German Ministry of Health, and a Duke-NUS Signature Research Program start-up grant (funded by the Agency for Science, Technology and Research of Singapore and the Ministry of Health of Singapore) to V. V. M., NIH grant R01 AI063476 to R. C., Armand-Frappier Foundation fellowships to N.S. and C. G., a postdoctoral fellowship by the German Research Foundation (DFG; GE2325/1-1) to I. G., funding from the Helmholtz-Alberta Initiative-Infectious Diseases Research (HAI-IDR) to E. G., and funding from the Helmholtz Virtual Institute VISTRIE (Viral Strategies of Immune Evasion) to M. D.