A RIG-I-like receptor directs antiviral responses to a bunyavirus and is antagonized by virus-induced blockade of TRIM25-mediated ubiquitination

The RIG-I-like receptors (RLRs) retinoic acid-inducible gene I protein (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) are cytosolic pattern recognition receptors that recognize specific viral RNA products and initiate antiviral innate immunity. Severe fever with thrombocytopenia sy...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	The Journal of biological chemistry Ročník 295; číslo 28; s. 9691
Hlavní autori:	Min, Yuan-Qin, Ning, Yun-Jia, Wang, Hualin, Deng, Fei
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 10.07.2020
Predmet:	A549 Cells DEAD Box Protein 58 - genetics DEAD Box Protein 58 - immunology HEK293 Cells Humans Immune Evasion Interferon-Induced Helicase, IFIH1 - genetics Interferon-Induced Helicase, IFIH1 - immunology Phlebovirus - genetics Phlebovirus - immunology Receptors, Immunologic Severe Fever with Thrombocytopenia Syndrome - genetics Severe Fever with Thrombocytopenia Syndrome - immunology Severe Fever with Thrombocytopenia Syndrome - pathology Signal Transduction - genetics Signal Transduction - immunology Transcription Factors - genetics Transcription Factors - immunology Tripartite Motif Proteins - genetics Tripartite Motif Proteins - immunology Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - immunology Ubiquitination - genetics Ubiquitination - immunology Viral Nonstructural Proteins - genetics Viral Nonstructural Proteins - immunology inclusion body (IB) nonstructural protein (NSs) virulence factor tripartite motif-containing 25 (TRIM25) severe fever with thrombocytopenia syndrome virus (SFTSV) virus-host interaction immune evasion innate immunity viral immunology infectious disease melanoma differentiation–associated protein 5 (MDA5) virology retinoic acid-inducible gene I protein (RIG-I)
ISSN:	1083-351X, 1083-351X
On-line prístup:	Zistit podrobnosti o prístupe
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Popis
Shrnutí:	The RIG-I-like receptors (RLRs) retinoic acid-inducible gene I protein (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) are cytosolic pattern recognition receptors that recognize specific viral RNA products and initiate antiviral innate immunity. Severe fever with thrombocytopenia syndrome virus (SFTSV) is a highly pathogenic member of the RIG-I, but not MDA5, has been suggested to sense some bunyavirus infections; however, the roles of RLRs in anti-SFTSV immune responses remain unclear. Here, we show that SFTSV infection induces an antiviral response accompanied by significant induction of antiviral and inflammatory cytokines and that RIG-I plays a main role in this induction by recognizing viral 5'-triphosphorylated RNAs and by signaling via the adaptor mitochondrial antiviral signaling protein. Moreover, MDA5 may also sense SFTSV infection and contribute to IFN induction, but to a lesser extent. We further demonstrate that the RLR-mediated anti-SFTSV signaling can be antagonized by SFTSV nonstructural protein (NSs) at the level of RIG-I activation. Protein interaction and MS-based analyses revealed that NSs interacts with the host protein tripartite motif-containing 25 (TRIM25), a critical RIG-I-activating ubiquitin E3 ligase, but not with RIG-I or Riplet, another E3 ligase required for RIG-I ubiquitination. NSs specifically trapped TRIM25 into viral inclusion bodies and inhibited TRIM25-mediated RIG-I-Lys-63-linked ubiquitination/activation, contributing to suppression of RLR-mediated antiviral signaling at its initial stage. These results provide insights into immune responses to SFTSV infection and clarify a mechanism of the viral immune evasion, which may help inform the development of antiviral therapeutics.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1083-351X 1083-351X
DOI:	10.1074/jbc.RA120.013973