Human Respiratory Syncytial Virus Nucleoprotein and Inclusion Bodies Antagonize the Innate Immune Response Mediated by MDA5 and MAVS
Open Access
- 1 August 2012
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 86 (15), 8245-8258
- https://doi.org/10.1128/jvi.00215-12
Abstract
Currently, the spatial distribution of human respiratory syncytial virus (hRSV) proteins and RNAs in infected cells is still under investigation, with many unanswered questions regarding the interaction of virus-induced structures and the innate immune system. Very few studies of hRSV have used subcellular imaging as a means to explore the changes in localization of retinoic-acid-inducible gene-I (RIG-I)-like receptors or the mitochondrial antiviral signaling (MAVS) protein, in response to the infection and formation of viral structures. In this investigation, we found that both RIG-I and melanoma differentiation-associated gene 5 (MDA5) colocalized with viral genomic RNA and the nucleoprotein (N) as early as 6 h postinfection (hpi). By 12 hpi, MDA5 and MAVS were observed within large viral inclusion bodies (IB). We used a proximity ligation assay (PLA) and determined that the N protein was in close proximity to MDA5 and MAVS in IBs throughout the course of the infection. Similar results were found with the transient coexpression of N and the phosphoprotein (P). Additionally, we demonstrated that the localization of MDA5 and MAVS in IBs inhibited the expression of interferon β mRNA 27-fold following Newcastle disease virus infection. From these data, we concluded that the N likely interacts with MDA5, is in close proximity to MAVS, and localizes these molecules within IBs in order to attenuate the interferon response. To our knowledge, this is the first report of a specific function for hRSV IBs and of the hRSV N protein as a modulator of the innate immune response.Keywords
This publication has 28 references indexed in Scilit:
- Multiple Functional Domains and Complexes of the Two Nonstructural Proteins of Human Respiratory Syncytial Virus Contribute to Interferon Suppression and Cellular LocationJournal of Virology, 2011
- Respiratory Syncytial Virus Induces Host RNA Stress Granules To Facilitate Viral ReplicationJournal of Virology, 2010
- Respiratory Syncytial Virus-Mediated NF-κB p65 Phosphorylation at Serine 536 Is Dependent on RIG-I, TRAF6, and IKKβJournal of Virology, 2010
- Pathogen Recognition and Inflammatory Signaling in Innate Immune DefensesClinical Microbiology Reviews, 2009
- Association of Respiratory Syncytial Virus M Protein with Viral Nucleocapsids Is Mediated by the M2-1 ProteinJournal of Virology, 2008
- Respiratory syncytial virus uses a Vps4-independent budding mechanism controlled by Rab11-FIP2Proceedings of the National Academy of Sciences of the United States of America, 2008
- Dynamics of filamentous viral RNPs prior to egressNucleic Acids Research, 2007
- Direct observation of individual endogenous protein complexes in situ by proximity ligationNature Methods, 2006
- Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-κB and IRF3Cell, 2005
- The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responsesNature Immunology, 2004