Hazara Orthonairovirus Nucleoprotein Antagonizes Type I Interferon Production by Inhibition of RIG-I Ubiquitination

Viruses. 2022 Sep 4;14(9):1965. doi: 10.3390/v14091965.

Abstract

Viruses have evolved various strategies to evade the host innate immune system. The relationship between nairoviruses and the interferon (IFN) system is poorly understood. We investigated whether and how nairoviruses antagonize host innate immunity using Hazara orthonairovirus (HAZV) as a surrogate model for Crimean-Congo hemorrhagic fever virus. HAZV nucleoprotein (N) was found to interact with the tripartite motif-containing protein 25 (TRIM25). The N-terminal region of N protein and the C-terminal region of TRIM25 are important for their interaction. Overexpression of N protein results in weakened interaction of TRIM25 with retinoic acid-inducible gene I (RIG-I). Furthermore, K63-linked polyubiquitination of RIG-I is inhibited in the presence of N protein. Our data collectively suggest that HAZV N protein interferes with the binding of TRIM25 to RIG-I and subsequent K63-linked polyubiquitination of RIG-I, which leads to inhibition of type I IFN production.

Keywords: Hazara orthonairovirus; N protein; interferon; retinoic acid-inducible gene I; tripartite motif-containing protein 25.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DEAD Box Protein 58 / genetics
  • Immunity, Innate
  • Interferon Type I* / metabolism
  • Nairovirus*
  • Nucleoproteins / metabolism
  • Tretinoin
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination

Substances

  • Interferon Type I
  • Nucleoproteins
  • Tretinoin
  • Ubiquitin-Protein Ligases
  • DEAD Box Protein 58

Grants and funding

This work was supported by Grant-in-Aid Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (20K07528). The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.