Interferon inducible porcine 2′, 5′-oligoadenylate synthetase like-1 protein limits porcine reproductive and respiratory syndrome virus 2 infection via the MDA5-mediated interferon-signaling pathway

Background: Porcine reproductive and respiratory syndrome virus 2 (PRRSV-2) is a constant threat to the swine industry worldwide. 2', 5'-oligoadenylate synthetase-like (OASL) protein has antiviral activity, but this has not been demonstrated for PRRSV-2, and the mechanism is not well elucidated. Results: In this study, the expression of OASL1 in porcine alveolar macrophages (PAMs) induced by interferon (IFN)-beta stimulation and PRRSV-2 infection was examined by quantitative real-time polymerase chain reaction and western blotting. Ectopic expression and knockdown of porcine OASL1 (pOASL1) indicated the role of OASL1 in PRRSV-2 replication cycle. Results showed that the expression of OASL1 in PAMs was significantly increased by IFN-beta stimulation or PRRSV-2 infection. OASL1 specific small interfering RNA promoted PRRSV-2 replication, whereas ectopic expression of pOASL1 inhibited PRRSV-2 infection. The mechanism revealed OASL1 interacts with Melanoma differentiation-associated protein 5 (MDA5) to increase IFN responses, and the antiPRRSV-2 activity was lost after the knockdown of the MDA5 RNA sensor. Conclusions: OASL1 inhibits PRRSV-2 infection via the activation of MDA5.

Automated summary

This study demonstrates that porcine OASL1 inhibits PRRSV-2 infection through activation of MDA5, providing new evidence for understanding the mechanism.