tetano
Editor, Senior Moderator
J Virol. 2011 Nov 9. [Epub ahead of print]
Chicken cells sense influenza A virus infection through MDA5 and CARDIF-signaling involving LGP2.
Liniger M, Summerfield A, Zimmer G, McCullough KC, Ruggli N.
Source
Institute of Virology and Immunoprophylaxis (IVI), Sensemattstrasse 293, CH-3147 Mittelh?usern, Switzerland.
Abstract
Avian influenza viruses (AIV) raise world-wide veterinary and public health concern 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. 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 chIFN-β promoter. 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, 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.
PMID:
22072756
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22072756
Chicken cells sense influenza A virus infection through MDA5 and CARDIF-signaling involving LGP2.
Liniger M, Summerfield A, Zimmer G, McCullough KC, Ruggli N.
Source
Institute of Virology and Immunoprophylaxis (IVI), Sensemattstrasse 293, CH-3147 Mittelh?usern, Switzerland.
Abstract
Avian influenza viruses (AIV) raise world-wide veterinary and public health concern 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. 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 chIFN-β promoter. 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, 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.
PMID:
22072756
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22072756