PubMed Journals: J Biol Chem
Source: PMID: 17204473
⇦ ⇨ J Biol Chem. 2007 Mar 9;282(10):7576-81.
⇩ Epub 2007 Jan 4.
Viral infections activate types I and III
interferon genes through a common mechanism.
Onoguchi K(1), Yoneyama M, Takemura A, Akira
S, Taniguchi T, Namiki H, Fujita T.
(1) Laboratory of Molecular Genetics, Institute
for Virus Research and Graduate School of
Biostudies, Kyoto University, Kyoto 606-8507,
Viral infections trigger innate immune responses,
including the production of type I interferons
(IFN-alpha and -beta) and other proinflammatory
cytokines. Novel antiviral cytokines IFN-lambda1,
IFN-lambda2, and IFN-lambda3 are classified
as type III IFNs and have evolved independently
of type I IFNs. Type III IFN genes are regulated
at the level of transcription and induced
by viral infection. Although the regulatory
mechanism of type I IFNs is well elucidated,
the expression mechanism of IFN-lambdas
is not well understood. Here, we analyzed
the mechanism by which IFN-lambda gene expression
is induced by viral infections. Loss- and
gain-of-function experiments revealed the
involvement of RIG-I (retinoic acid-inducible
gene I), IPS-1, TBK1, and
interferon regulatory factor-3, key regulators
of the virus-induced activation of type
I IFN genes. Consistent with this, a search
for the cis-regulatory element of the human
ifnlambda1 revealed a cluster of interferon
regulatory factor-binding sites and a
NF-kappaB-binding site. Functional analysis
demonstrated that all of these sites are
essential for gene activation by the virus.
These results strongly suggest that types
I and III IFN genes are regulated by a common
DOI: 10.1074/jbc.M608618200 PMID: 17204473
[Indexed for MEDLINE]