Thogoto virus ML protein suppresses IRF3 function

Journal Article · Wed Jan 05 04:00:00 EST 2005 · Virology

DOI:https://doi.org/10.1016/j.virol.2004.10.015· OSTI ID:20637191

Jennings, Stephanie ^[1]; Martinez-Sobrido, Luis ^[2]; Garcia-Sastre, Adolfo ^[2]; Weber, Friedemann ^[1]; Kochs, Georg ^[1]

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1. Abteilung Virologie, Institut fuer Medizinische Mikrobiologie und Hygiene, Universitaet Freiburg, D-79008 Freiburg (Germany)
2. Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029 (United States)

The Thogoto virus (THOV) is a member of the family Orthomyxoviridae. It prevents induction of alpha/beta interferons (IFN) in cell culture and in vivo via the action of the viral ML protein. Phenotypically, the effect of THOV ML resembles that of the NS1 protein of influenza A virus (FLUAV) in that it blocks the expression of IFN genes. IFN expression depends on IFN regulatory factor 3 (IRF3). Upon activation, IRF3 forms homodimers and accumulates in the nucleus where it binds the transcriptional coactivator CREB-binding protein (CBP). Here, we show that expression of ML blocked the transcriptional activity of IRF3 after stimulation by virus infection. Further biochemical analysis revealed that ML acts by blocking IRF3 dimerization and association with CBP. Surprisingly, however, ML did not interfere with the nuclear transport of IRF3. Thus, the action of ML differs strikingly from that of FLUAV NS1 that prevents IFN induction by retaining IRF3 in the cytoplasm.

• OSTI ID: 20637191
• Journal Information: Virology, Journal Name: Virology Journal Issue: 1 Vol. 331; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL CULTURES
CYTOPLASM
DIMERIZATION
GENES
IN VIVO
INFLUENZA
INFLUENZA VIRUSES
INTERFERON
LUCIFERASE
NEWCASTLE DISEASE
RNA
STIMULATION