STAT Protein Interference and Suppression of Cytokine Signal Transduction by Measles Virus V Protein

• DOI: 10.1128/jvi.77.13.7635-7644.2003
• Publication Date: 2003-06-13T00:18:39Z
• Authors: Heidi Palosaari; Jean-Patrick Pari...; Jason J. Rodriguez; Christina M. Ulane; Curt M. Horvath
• Keywords: STAT2; Morbillivirus; Mononegavirales; STAT1

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