Chicken Cells Sense Influenza A Virus Infection through MDA5 and CARDIF Signaling Involving LGP2
Open Access
- 15 January 2012
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 86 (2), 705-717
- https://doi.org/10.1128/jvi.00742-11
Abstract
Avian influenza viruses (AIV) raise worldwide veterinary and public health concerns due to their potential for zoonotic transmission. While infection with highly pathogenic AIV results in high mortality in chickens, this is not necessarily the case in wild birds and ducks. It is known that innate immune factors can contribute to the outcome of infection. In this context, retinoic acid-inducible gene I (RIG-I) is the main cytosolic pattern recognition receptor known for detecting influenza A virus infection in mammalian cells. Chickens, unlike ducks, lack RIG-I, yet chicken cells do produce type I interferon (IFN) in response to AIV infection. Consequently, we sought to identify the cytosolic recognition elements in chicken cells. Chicken mRNA encoding the putative chicken analogs of CARDIF and LGP2 (chCARDIF and chLGP2, respectively) were identified. HT7-tagged chCARDIF was observed to associate with mitochondria in chicken DF-1 fibroblasts. The exogenous expression of chCARDIF, as well as of the caspase activation and recruitment domains (CARDs) of the chicken melanoma differentiation-associated protein 5 (chMDA5), strongly activated the chicken IFN-β (chIFN-β) promoter. The silencing of chMDA5, chCARDIF, and chIRF3 reduced chIFN-β levels induced by AIV, indicating their involvement in AIV sensing. As with mammalian cells, chLGP2 had opposing effects. While overexpression decreased the activation of the chIFN-β promoter, the silencing of endogenous chLGP2 reduced chIFN-β induced by AIV. We finally demonstrate that the chMDA5 signaling pathway is inhibited by the viral nonstructural protein 1. In conclusion, chicken cells, including DF-1 fibroblasts and HD-11 macrophage-like cells, employ chMDA5 for sensing AIV.Keywords
This publication has 62 references indexed in Scilit:
- Recognition of viral nucleic acids in innate immunityReviews in Medical Virology, 2009
- H5N1 influenza viruses: outbreaks and biological propertiesCell Research, 2009
- 5′-triphosphate RNA requires base-paired structures to activate antiviral signaling via RIG-IProceedings of the National Academy of Sciences of the United States of America, 2009
- Recognition of 5′ Triphosphate by RIG-I Helicase Requires Short Blunt Double-Stranded RNA as Contained in Panhandle of Negative-Strand VirusImmunity, 2009
- Influenza A Virus NS1 Targets the Ubiquitin Ligase TRIM25 to Evade Recognition by the Host Viral RNA Sensor RIG-ICell Host & Microbe, 2009
- Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virusNature, 2005
- VISA Is an Adapter Protein Required for Virus-Triggered IFN-β SignalingMolecular Cell, 2005
- Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-κB and IRF3Cell, 2005
- IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon inductionNature Immunology, 2005
- The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responsesNature Immunology, 2004