Nonstructural Protein NSs Hampers Cellular Antiviral Response through LSm14A during Severe Fever with Thrombocytopenia Syndrome Virus Infection
| Autor: | Yajie Guan, Yuxuan Fu, Rui Zhang, Nan Zheng, Li Zhang, Na Jiang, Zhiwei Wu |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Phlebovirus Proteomics Cell type Severe Fever with Thrombocytopenia Syndrome Immunology Biology Viral Nonstructural Proteins Antiviral Agents Cell Line Mice Viral life cycle Cell Line Tumor Immunology and Allergy Animals Humans Phosphorylation Host protein Gene knockdown Innate immune system Proteomic screening Interferon-beta Virology Immunity Innate Mice Inbred C57BL HEK293 Cells Ribonucleoproteins Host-Pathogen Interactions Interferon Regulatory Factor-3 Severe fever with thrombocytopenia syndrome virus HeLa Cells Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 207(2) |
| ISSN: | 1550-6606 |
| Popis: | The nonstructural protein (NSs) of severe fever with thrombocytopenia syndrome virus (SFTSV) plays multiple functions in the virus life cycle. Proteomic screening for host proteins interacting with NSs identified the cellular protein LSm14A. LSm14A, a member of the LSm family involved in RNA processing in the processing bodies, binds to viral RNA or synthetic homolog and mediates IFN regulatory factor 3 activation and IFN-β induction. NSs interacted with and colocalized with LSm14A, and this interaction effectively inhibited downstream phosphorylation and dimerization of IFN regulatory factor 3, resulting in the suppression of antiviral signaling and IFN induction in several cell types of human origin. Knockdown of NSs resulted in the suppression of SFTSV replication in host cells. Viral RNA bound to LSm14A–NSs protein complex during the interaction. A newly discovered LRRD motif of NSs functioned to interact with LSm14A. Altogether, our data demonstrated a mechanism used by SFTSV to inhibit host innate immune response. |
| Databáze: | OpenAIRE |
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