Elsevier

Virus Research

Volume 268, 15 July 2019, Pages 18-26
Virus Research

Nucleotide-binding oligomerization domain-like receptor X1 restricts porcine reproductive and respiratory syndrome virus-2 replication by interacting with viral Nsp9

https://doi.org/10.1016/j.virusres.2019.05.011Get rights and content

Highlights

  • PRRSV infection up-regulates NLRX1 expression.

  • NLRX1 impairs PRRSV replication.

  • NLRX1 suppresses the synthesis of viral subgenomic RNAs.

  • NLRX1 interacts and colocalizes with the Nsp9 of PRRSV.

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) causes one of the most economically important diseases of swine worldwide. Current antiviral strategies provide only limited protection. Nucleotide-binding oligomerization domain-like receptor (NLR) X1 is unique among NLR proteins in its functions as a pro-viral or antiviral factor to different viral infections. To date, the impact of NLRX1 on PRRSV infection remains unclear. In this study, we found that PRRSV infection promoted the expression of NLRX1 gene. In turn, ectopic expression of NLRX1 inhibited PRRSV replication in Marc-145 cells, whereas knockdown of NLRX1 enhanced PRRSV propagation in porcine alveolar macrophages (PAMs). Mechanistically, NLRX1 was revealed to impair intracellular viral subgenomic RNAs accumulation. Finally, Mutagenic analyses indicated that the LRR (leucine-rich repeats) domain of NLRX1 interacted with PRRSV Nonstructural Protein 9 (Nsp9) RdRp (RNA-dependent RNA Polymerase) domain and was necessary for antiviral activity. Thus, our study establishes the role of NLRX1 as a new host restriction factor in PRRSV infection.

Keywords

Porcine reproductive and respiratory syndrome virus (PRRSV)
Nonstructural Protein 9 (Nsp9)
Nucleotide-binding oligomerization domain-like receptor X1 (NLRX1)
PRRSV-host interactions
Replication

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