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 Döring, Ulrich Kalinke, Danielle E. Anderson, Roberto Cattaneo, Veronika Von Messling

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 deficiencies was also generated, and available wild-type and V-protein-knockout viruses were used as controls. Ferrets infected with wild-type and STAT1-blind viruses developed severe leukopenia and loss of lymphocyte proliferation activity and succumbed to the disease within 14 days. In contrast, animals infected with viruses with STAT2 or mda5 defect or both STAT2 and mda5 defects developed a mild self-limiting disease similar to that associated with the V-knockout virus. This study demonstrates the importance of interference with STAT2 and mda5 signaling for CDV immune evasion and provides a starting point for the development of morbillivirus vectors with reduced immunosuppressive properties.

Original languageEnglish (US)
Pages (from-to)2941-2950
Number of pages10
JournalJournal of Virology
Volume88
Issue number5
DOIs
StatePublished - Mar 2014

Fingerprint

Morbillivirus
Canine Distemper Virus
STAT1 Transcription Factor
Ferrets
Canine distemper virus
ferrets
interferons
melanoma
Interferons
Virulence
virulence
Viruses
proteins
Innate Immunity
viruses
Immune Evasion
Protein Deficiency
Proteins
Leukopenia
Immunosuppressive Agents

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Svitek, N., Gerhauser, I., Goncalves, C., Grabski, E., Döring, M., Kalinke, U., ... Von Messling, V. (2014). Morbillivirus control of the interferon response: Relevance of STAT2 and mda5 but not STAT1 for canine distemper virus virulence in ferrets. Journal of Virology, 88(5), 2941-2950. https://doi.org/10.1128/JVI.03076-13

Morbillivirus control of the interferon response : Relevance of STAT2 and mda5 but not STAT1 for canine distemper virus virulence in ferrets. / Svitek, Nicholas; Gerhauser, Ingo; Goncalves, Christophe; Grabski, Elena; Döring, Marius; Kalinke, Ulrich; Anderson, Danielle E.; Cattaneo, Roberto; Von Messling, Veronika.

In: Journal of Virology, Vol. 88, No. 5, 03.2014, p. 2941-2950.

Research output: Contribution to journalArticle

Svitek, N, Gerhauser, I, Goncalves, C, Grabski, E, Döring, M, Kalinke, U, Anderson, DE, Cattaneo, R & Von Messling, V 2014, 'Morbillivirus control of the interferon response: Relevance of STAT2 and mda5 but not STAT1 for canine distemper virus virulence in ferrets', Journal of Virology, vol. 88, no. 5, pp. 2941-2950. https://doi.org/10.1128/JVI.03076-13
Svitek, Nicholas ; Gerhauser, Ingo ; Goncalves, Christophe ; Grabski, Elena ; Döring, Marius ; Kalinke, Ulrich ; Anderson, Danielle E. ; Cattaneo, Roberto ; Von Messling, Veronika. / Morbillivirus control of the interferon response : Relevance of STAT2 and mda5 but not STAT1 for canine distemper virus virulence in ferrets. In: Journal of Virology. 2014 ; Vol. 88, No. 5. pp. 2941-2950.
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