The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I
Authors
Rothenfusser, SimonGoutagny, Nadege
DiPerna, Gary
Gong, Mei
Monks, Brian G.
Schoenemeyer, Annett
Yamamoto, Masahiro
Akira, Shizuo
Fitzgerald, Katherine A.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2005-10-08Keywords
Adaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular Transport
Animals
Antigens, Differentiation
Cell Line
Humans
Membrane Transport Proteins
Mice
Mice, Knockout
Myelin Proteins
Myeloid Differentiation Factor 88
Proteolipids
RNA Helicases
RNA, Double-Stranded
Receptors, Immunologic
Sendai virus
Signal Transduction
TNF Receptor-Associated Factor 6
Toll-Like Receptor 3
Toll-Like Receptors
Trans-Activators
Virus Replication
Immunology and Infectious Disease
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
The paramyxovirus Sendai (SV), is a well-established inducer of IFN-alphabeta gene expression. In this study we show that SV induces IFN-alphabeta gene expression normally in cells from mice with targeted deletions of the Toll-IL-1 resistance domain containing adapters MyD88, Mal, Toll/IL-1R domain-containing adaptor inducing IFN-beta (TRIF), and TRIF-related adaptor molecule TLR3, or the E3 ubiquitin ligase, TNFR-associated factor 6. This TLR-independent induction of IFN-alphabeta after SV infection is replication dependent and mediated by the RNA helicase, retinoic acid-inducible gene-I (RIG-I) and not the related family member, melanoma differentiation-associated gene 5. Furthermore, we characterize a RIG-I-like RNA helicase, Lgp2. In contrast to RIG-I or melanoma differentiation-associated gene 5, Lgp2 lacks signaling caspase recruitment and activation domains. Overexpression of Lgp2 inhibits SV and Newcastle disease virus signaling to IFN-stimulated regulatory element- and NF-kappaB-dependent pathways. Importantly, Lgp2 does not prevent TLR3 signaling. Like RIG-I, Lgp2 binds double-stranded, but not single-stranded, RNA. Quantitative PCR analysis demonstrates that Lgp2 is present in unstimulated cells at a lower level than RIG-I, although both helicases are induced to similar levels after virus infection. We propose that Lgp2 acts as a negative feedback regulator of antiviral signaling by sequestering dsRNA from RIG-I.Source
J Immunol. 2005 Oct 15;175(8):5260-8.
DOI
10.4049/jimmunol.175.8.5260Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38215PubMed ID
16210631Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.175.8.5260