MicroRNA 373 Facilitates the Replication of Porcine Reproductive and Respiratory Syndrome Virus by Its Negative Regulation of Type I Interferon Induction

Abstract

MicroRNAs (miRNAs) play an important role in the regulation of immune responses. Previous studies have indicated that dysregulating the miRNAs leads to the immunosuppression of porcine reproductive and respiratory syndrome virus (PRRSV). However, it is not clear how PRRSV regulates the expression of host miRNA, which may lead to immune escape or promote the replication of the virus. The present work suggests that PRRSV upregulated the expression of miR-373 through elevating the expression of specificity protein 1 (Sp1) in MARC-145 cells. Furthermore, this work demonstrated that miR-373 promoted the replication of PRRSV, since miR-373 was a novel negative miRNA for the production of beta interferon (IFN-␤) by targeting nuclear factor IA (NFIA), NFIB, interleukin-1 receptor-associated kinase 1 (IRAK1), IRAK4, and interferon regulatory factor 1 (IRF1). We also found that both NFIA and NFIB were novel proteins for inducing the production of IFN-␤, and both of them could inhibit the replication of PRRSV. In conclusion, PRRSV upregulated the expression of miR-373 by elevating the expression of Sp1 and hijacked the host miR-373 to promote the replication of PRRSV by negatively regulating the production of IFN-␤.IMPORTANCE PRRSV causes one of the most economically devastating diseases of swine, and there is no effective method for controlling PRRSV. It is not clear how PRRSV inhibits the host's immune response and induces persistent infection. Previous studies have shown that PRRSV inhibited the production of type I IFN, and the treatment of type I IFN could efficiently inhibit the replication of PRRSV, so it will be helpful to design new methods of controlling PRRSV by understanding the molecular mechanism by which PRRSV modulated the production of IFN. The current work shows that miR-373, upregulated by PRRSV, promotes PRRSV replication, since miR-373 impaired the production of IFN-␤ by targeting NFIA, NFIB, IRAK1, IRAK4, and IRF1, and both NFIA and NFIB were antiviral proteins to PRRSV. In conclusion, this paper revealed a novel mechanism of PRRSV that impaired the production of type I IFN by upregulating miR-373 expression in MARC-145 cells.

Deep RNA Sequencing Reveals a Repertoire of Human Fibroblast Circular RNAs Associated with Cellular Responses to Herpes Simplex Virus 1 Infection

“…Some small RNAs could be induced or exploited by viruses to favor the viral infection and persistence by attenuating the immune response, ceasing cell apoptosis, and promoting cell growth [52][53][54]. Interestingly, this strategy, as employed by a virus, was observed in HSV-1 and its host interactions [55][56][57]. Based on the roles of miRNAs during HSV-1 infection, we presumed that circRNAs functioned as miRNA sponges to indirectly regulate the host transcriptional responses.…”

Cellular microRNA miR-c89 inhibits replication of porcine reproductive and respiratory syndrome virus by targeting the host factor porcine retinoid X receptor β

“…Alternatively, some miRNAs also facilitate PRRSV infection. MicroRNA 373 aids PRRSV replication through the negative regulation of type I interferons [31], while miR-24-3p promotes PRRSV replication through the suppression of HO-1 expression [32].…”

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

“…miRNA-146a and miRNA-373: miR-146a is also up-regulated during PRRSV infection (Chen et al, 2017a). Since miR-146a is a negative regulator of immune responses, the upregulation of miR-146a may facilitate PRRSV infection.…”

“…Since miR-146a is a negative regulator of immune responses, the upregulation of miR-146a may facilitate PRRSV infection. PRRSV upregulates the expression of miR-373 by elevating the expression of specificity protein 1 (Sp1) in MARC-145 cells (Chen et al, 2017a). miR-373 is a negative regulator for IFN-β by targeting nuclear factor IA (NFIA), NFIB, interleukin-1 receptor-associated kinase 1 (IRAK1), IRAK4, and interferon regulatory factor 1 (IRF1), therefore miR-373 promotes PRRSV replication.…”

“…Viral infection can either activate or inhibit autophagy in cells. PRRSV induces autophagy to promote virus replication (Chen et al, 2017a;Chen et al, 2012;Li et al, 2016b;Liu et al, 2012;Sun et al, 2012a;Wang et al, 2015b), and the inhibition of autophagosome formation using siRNA leads to decreased yield of PRRSV (Chen et al, 2012;Sun et al, 2012a), and increased apoptosis ), suggesting that the autophagy induction by PRRSV promotes virus replication and protects the host cells from cell death. In MARC-145 cells, autophagy can favor PRRSV replication by postponing apoptosis through the formation of a Bad-Beclin1 complex .…”