Nuclear localization signal in TRIM22 is essential for inhibition of type 2 porcine reproductive and respiratory syndrome virus replication in MARC-145 cells

Abstract

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.

Molecular and Cellular Mechanisms for PRRSV Pathogenesis and Host Response to Infection

“…TRIM25 also inhibits PRRSV replication whereas the N protein antagonizes the antiviral activity by interfering with TRIM25-mediated RIG-I ubiquitination (Zhao et al, 2019). TRIM22 can also reduce PRRSV replication through interacting with N protein nuclear localization signal (Jing et al, 2019b).…”

The Function of the PRRSV–Host Interactions and Their Effects on Viral Replication and Propagation in Antiviral Strategies

“…Study has indicated that the PRRSV-2 N protein can antagonize the antiviral activity of TRIM25 and suppress innate immune responses of the host by competitively interacting with TRIM25, thereby interfering with TRIM25-mediated retinoic acid-inducible gene I (RIG-I) ubiquitination and inhibiting IFN-β production [ 38 ]. TRIM22 can interact with the PRRSV-2 N protein and reduce virus replication, and the SPla and the RYanodine Receptor (SPRY) domain and nuclear localization signal of TRIM22 are indispensable for this interaction [ 39 ]. Moreover, the N-terminal RING domain of TRIM59, which is an important antiviral component, can interact with the C-terminal NendoU domain of nsp11, thereby inhibiting PRRSV-2 infection [ 40 ].…”

“…With the rapid development of CRISPR/Cas-based gene editing technology, the acquisition of gene-edited pigs is no longer a difficult task. In this context, the TRIM22 gene has been lost during evolution, and restoring TRIM22 through gene editing will be a potential antiviral strategy [ 39 ]. Furthermore, gene-editing of CD163, which has been determined to be the major receptor, generates pigs resisting PRRSV infection [ 61 ].…”

Porcine TRIM21 Enhances Porcine Circovirus 2 Infection and Host Immune Responses, But Inhibits Apoptosis of PCV2-Infected Cells

“…At present, there are few studies on porcine TRIMs participating in virus infection and regulating the immune response. For example, it was reported that the nuclear localization signal of porcine TRIM22 plays a key role in inhibiting type 2 porcine reproductive and respiratory syndrome virus (PRRSV) replication [22], and porcine TRIM21 RING-finger E3 ubiquitin ligase is critical for anti-PRRSV activity [15]. TRIM21 inhibits porcine epidemic diarrhea virus replication by proteasomal degradation of the viral nucleocapsid protein [23], while TRIM21 suppresses foot-and-mouth disease virus (FMDV) infection via specific antibodymediated intracellular neutralization [24].…”