PubMed Journals: J Biol Chem
Source: PMID: 19380580
⇦ ⇨ J Biol Chem. 2009 Jun 12;284(24):16202-9.
⇩ doi: 10.1074/jbc.M109.008227. Epub 2009 Apr
Severe acute respiratory syndrome coronavirus
M protein inhibits type I interferon production
by impeding the formation of
Siu KL(1), Kok KH, Ng MH, Poon VK, Yuen
KY, Zheng BJ, Jin DY.
(1) Department of Biochemistry,
The University of Hong Kong, Pokfulam,
Severe acute respiratory syndrome (SARS)
coronavirus is highly pathogenic in humans
and evades innate immunity at multiple levels.
It has evolved various strategies to counteract
the production and action of type I interferons,
which mobilize the front-line defense against
viral infection. In this study we demonstrate
that SARS coronavirus M protein inhibits
gene transcription of type I interferons.
M protein potently antagonizes the activation
of interferon-stimulated response element-dependent
transcription by double-stranded RNA, RIG-I,
MDA5, TBK1, IKKepsilon, and
virus-induced signaling adaptor (VISA) but has
no influence on the transcriptional activity of this
element when IRF3 or IRF7 is overexpressed.
M protein physically associates with RIG-I,
TBK1, IKKepsilon, and TRAF3 and likely sequesters
some of them in membrane-associated cytoplasmic
compartments. Consequently, the expression
of M protein prevents the formation of
TRAF3.TANK.TBK1/IKKepsilon complex and thereby
inhibits TBK1/IKKepsilon-dependent activation of
IRF3/IRF7 transcription factors. Taken together,
our findings reveal a new mechanism by which
SARS coronavirus circumvents the production
of type I interferons.
DOI: 10.1074/jbc.M109.008227 PMCID: PMC2713514
PMID: 19380580 [Indexed for MEDLINE]