Hijacking of RIG-I signaling proteins into virus-induced cytoplasmic structures correlates with the inhibition of type I interferon responses

Felix W. Santiago, Lina M. Covaleda, Maria T. Sanchez-Aparicio, Jesus A. Silvas, Ana C. Diaz-Vizarreta, Jenish R. Patel, Vsevolod Popov, Xue Jie Yu, Adolfo García-Sastre, Patricia V. Aguilar

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Recognition of viral pathogens by the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family results in the activation of type I interferon (IFN) responses. To avoid this response, most viruses have evolved strategies that target different essential steps in the activation of host innate immunity. In this study, we report that the nonstructural protein NSs of the newly described severe fever with thrombocytopenia syndrome virus (SFTSV) is a potent inhibitor of IFN responses. The SFTSV NSs protein was found to inhibit the activation of the beta interferon (IFN-β) promoter induced by viral infection and by a RIG-I ligand. Astonishingly, we found that SFTSV NSs interacts with and relocalizes RIG-I, the E3 ubiquitin ligase TRIM25, and TANK-binding kinase 1 (TBK1) into SFTSV NSs-induced cytoplasmic structures. Interestingly, formation of these SFTSV NSs-induced structures occurred in the absence of the Atg7 gene, a gene essential for autophagy. Furthermore, confocal microscopy studies revealed that these SFTSV NSs-induced structures colocalize with Rab5 but not with Golgi apparatus or endoplasmic reticulum markers. Altogether, the data suggest that sequestration of RIG-I signaling molecules into endosome-like structures may be the mechanism used by SFTSV to inhibit IFN responses and point toward a novel mechanism for the suppression of IFN responses.

Original languageEnglish (US)
Pages (from-to)4572-4585
Number of pages14
JournalJournal of virology
Volume88
Issue number8
DOIs
StatePublished - Apr 2014

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Santiago, F. W., Covaleda, L. M., Sanchez-Aparicio, M. T., Silvas, J. A., Diaz-Vizarreta, A. C., Patel, J. R., Popov, V., Yu, X. J., García-Sastre, A., & Aguilar, P. V. (2014). Hijacking of RIG-I signaling proteins into virus-induced cytoplasmic structures correlates with the inhibition of type I interferon responses. Journal of virology, 88(8), 4572-4585. https://doi.org/10.1128/JVI.03021-13