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.
Porcine reproductive and respiratory syndrome virus (PRRSV) infection causes one of the most economically important swine diseases worldwide. Tripartite motif-containing 22 (TRIM22), a TRIM family protein, has been identified as a crucial restriction factor that inhibits a group of human viruses. Currently, the role of cellular TRIM22 in PRRSV infection remains unclear. In the present study, we analyzed the effect of TRIM22 on PRRSV replication in vitro and explored the underlying mechanism. Ectopic expression of TRIM22 impaired the viral replication, while TRIM22-RNAi favored the replication of PRRSV in MARC-145 cells. Additionally, we observed that TRIM22 deletion SPRY domain or Nuclear localization signal (NLS) losses the ability to inhibit PRRSV replication. Finally, Co-IP analysis identified that TRIM22 interacts with PRRSV nucleocapsid (N) protein through the SPRY domain, while the NLS2 motif of N protein is involved in interaction with TRIM22. Although the concentration of PRRSV N protein was not altered in the presence of TRIM22, the abundance of N proteins from simian hemorrhagic fever virus (SHFV), equine arteritis virus (EAV), and murine lactate dehydrogenaseelevating virus (LDV) diminished considerably with increasing TRIM22 expression. Together, our findings uncover a previously unrecognized role for TRIM22 and extend the antiviral effects of TRIM22 to arteriviruses.Keywords Porcine reproductive and respiratory syndrome virus (PRRSV) · Nucleocapsid (N) protein · Tripartite motifcontaining 22 (TRIM22) · PRRSV-host interaction · Replication Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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