Influenza A Virus Inhibits Type I IFN Signaling via NF-κB-Dependent Induction of SOCS-3 Expression

• DOI: 10.1371/journal.ppat.1000196
• Publication Date: 2008-11-06T22:57:53Z
• Authors: Eva-K. Pauli; Mirco Schmolke; Thorsten Wolff; Dorothee Viemann; Johannes Roth; Johannes G. Bode; Stephan Ludwig
• Keywords: 0301 basic medicine; Interferon Type I/pharmacology; QH301-705.5; Immunology; 610 Medizin; 610; Suppressor of Cytokine Signaling Proteins; Influenza A virus/physiology*; Virus Replication; Microbiology; Cell Line; 03 medical and health sciences; Suppressor of Cytokine Signaling Proteins/genetics*; Virology; Gene Expression Regulation*; Genetics; Animals; Humans; RNA, Messenger; Biology (General); Phosphorylation; Molecular Biology; ddc:610; Interferon Type I/antagonists & inhibitors*; NF-kappa B; Signal Transduction*; NF-kappa B/metabolism*; RC581-607; Messenger/analysis; 3. Good health; STAT1 Transcription Factor; Gene Expression Regulation; Influenza A virus; Suppressor of Cytokine Signaling 3 Protein; Interferon Type I; RNA; Parasitology; STAT1 Transcription Factor/metabolism; Immunologic diseases. Allergy; Research Article; Signal Transduction

The type I interferon (IFN) system is a first line of defense against viral infections. Viruses have developed various mechanisms to counteract this response. So far, the antagonistic activity influenza A viruses was mainly observed on level IFNβ gene induction via action non-structural protein 1 (NS1). Here we present data indicating that not only suppress but also inhibit IFN signaling through mechanism involving suppressor cytokine signaling-3 (SOCS-3) protein. Our study based observation in cells were infected with virus and subsequently stimulated IFNα/β, phosphorylation signal transducer activator transcription (STAT1) strongly reduced. This impaired STAT1 activation due proteins rather appeared be induced by accumulation 5′ triphosphate RNA cell. SOCS are potent endogenous inhibitors Janus kinase (JAK)/STAT signaling. Closer examination revealed SOCS-3 SOCS-1 mRNA levels increase an RNA- nuclear factor kappa B (NF-κB)-dependent IFN-independent manner early replication cycle. direct expression appears relevant for suppression antiviral response since deficient sustained correlated elevated IFN-dependent genes. As consequence, progeny titers reduced or knocked-down siRNA. These provide evidence JAK/STAT activation. inhibitory effect at least part expression, which results