Stat protein interference and suppression of cytokine signal transduction by measles virus V protein

Heidi Palosaari, Jean Patrick Parisien, Jason J. Rodriguez, Christina M. Ulane, Curt M. Horvath*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

225 Scopus citations

Abstract

Measles virus, a paramyxovirus of the Morbillivirus genus, is responsible for an acute childhood illness that infects over 40 million people and leads to the deaths of more than 1 million people annually (C. J. Murray and A. D. Lopez, Lancet 349:1269-1276, 1997). Measles virus infection is characterized by virus-induced immune suppression that creates susceptibility to opportunistic infections. Here we demonstrate that measles virus can inhibit cytokine responses by direct interference with host STAT protein-dependent signaling systems. Expression of the measles V protein prevents alpha, beta, and gamma interferon-induced transcriptional responses. Furthermore, it can interfere with signaling by interleukin-6 and the non-receptor tyrosine kinase, v-Src. Affinity purification demonstrates that the measles V protein associates with cellular STAT1, STAT2, STAT3, and IRF9, as well as several unidentified partners. Mechanistic studies indicate that while the measles V protein does not interfere with STAT1 or STAT2 tyrosine phosphorylation, it causes a defect in IFN-induced STAT nuclear accumulation. The defective STAT nuclear redistribution is also observed in measles virus-infected cells, where some of the STAT protein is detected in cytoplasmic bodies that contain viral nucleocapsid protein and nucleic acids. Interference with STAT-inducible transcription may provide a novel intracellular mechanism for measles virus-induced cytokine inhibition that links innate immune evasion to adaptive immune suppression.

Original languageEnglish (US)
Pages (from-to)7635-7644
Number of pages10
JournalJournal of virology
Volume77
Issue number13
DOIs
StatePublished - Jul 2003

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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