Viral infections activate types I and III interferon genes through a common mechanism.
J Biol Chem
; 282(10): 7576-81, 2007 Mar 09.
Article
em En
| MEDLINE
| ID: mdl-17204473
ABSTRACT
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 mechanism.
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Base de dados:
MEDLINE
Assunto principal:
Viroses
/
Interferon Tipo I
/
Regulação da Expressão Gênica
/
Citocinas
/
Interleucinas
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article