MicroRNA-376b-3p Promotes Porcine Reproductive and Respiratory Syndrome Virus Replication by Targeting Viral Restriction Factor TRIM22

Abstract

Porcine reproductive and respiratory syndrome virus is a major economically significant pathogen and has evolved several strategies to evade host's antiviral response and provide favorable conditions for survival. In the present study, we demonstrated that a host microRNA, miR-376b-3p, was upregulated by PRRSV infection through the viral components, nsp4 and nsp11, and miR-376b-3p can directly target tripartite motif-containing 22 (TRIM22) to impair its anti-PRRSV activity, thus facilitating the replication of PRRSV. Meanwhile, we found that TRIM22 induced degradation of the nucleocapsid protein (N) of PRRSV by interacting with N protein to inhibit PRRSV replication, and further study indicated that TRIM22 could enhance the activation of lysosomal pathway by interacting with LC3 to induce lysosomal degradation of N protein. In conclusion, PRRSV increased miR-376b-3p expression and hijacked the host miR-376b-3p to promote PRRSV replication by impairing the antiviral effect of TRIM22. Therefore, our finding outlines a novel strategy of immune evasion exerted by PRRSV, which is helpful for better understanding the pathogenesis of PRRSV. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) causes enormous economic losses each year in the swine industry worldwide. MicroRNAs (miRNAs) play important roles during viral infections via modulating the expression of viral or host genes at post-transcriptional level. TRIM22 has recently been identified as a key restriction factor that inhibited the replication of a number of human virus such as HIV, ECMV, HCV, HBV, IAV, and RSV. Here we showed that host miR-376b-3p could be up-regulated by PRRSV and functioned to impair the anti-PRRSV role of TRIM22 to facilitate PRRSV replication. Meanwhile, we found that TRIM22 inhibited the replication of PRRSV by interacting with viral N protein and accelerating its degradation through the lysosomal pathway. Collectively, the paper described a novel mechanism that PRRSV exploited the host miR-376b-3p to evade antiviral responses and provided a new insight into the study of virus-host interactions.

Porcine Reproductive and Respiratory Syndrome Virus Modulates the Switch of Macrophage Polarization from M1 to M2 by Upregulating MoDC-Released sCD83

“…Porcine reproductive and respiratory syndrome virus (PRRSV), a virulent pathogen of swine, suppresses the innate immune response and induces persistent infection [ 5 , 50 , 51 ]. More detailed reviews of host interactions with PRRSV conclude that most PRRSV strains delayed and impaired the adaptive immune response, inhibiting the release of pro-inflammatory cytokines, promoting anti-inflammatory cytokines, and modulating the activity and function of immune cells, including dendritic cells, macrophages, natural killer cells, T lymphocytes, and B lymphocytes [ 1 , 3 , 5 , 13 , 14 ].…”

Inducible miR-150 Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication by Targeting Viral Genome and Suppressor of Cytokine Signaling 1

“…Besides affecting type I IFN signaling, miR-22 promotes PRRSV replication through targeting host factor HO-1 [ 54 ]. Additionally, miR-376b-3p, as a pro-viral miRNA, was involved in the lysosomal pathway by targeting TRIM22 [ 55 ]. Based on numerous studies, miRNAs have the potential use to control PRRSV.…”

Role of microRNAs in host defense against porcine reproductive and respiratory syndrome virus infection: a hidden front line

“…It was reported that the expression of miR-376b-3p is remarkably increased in PRRSV-infected MARC-145 cells, and this upregulation facilitated the PRRSV replication and inhibited the tripartite motif-containing 22 (TRIM22) expression via targeting its 3’ UTR, impairing TRIM22-mediated anti-PRRSV activity ( Figure 2B , Table 1 ) ( 102 ). TRIM22 as a key restriction can inhibit PRRSV replication thought interacting with the N protein ( 103 ).…”