Interferon Inducible Porcine 2′, 5′-oligoadenylate Synthetase-Like Protein Limits Porcine Reproductive and Respiratory Syndrome Virus Infection via the MDA5-Mediated Interferon-Signaling Pathway

Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is a constant threat to the swine industry worldwide. Currently approved vaccines against PRRSV are losing effectiveness, as new viral strains are often refractory to conventional treatments. Thus, there is an urgent need to find new therapeutic targets to develop novel antiviral drugs. 2′, 5′-oligoadenylate synthetase-like (OASL) protein has antiviral activity, but this has not been demonstrated for PRRSV and the mechanism is not well elucidated. In this study expression of porcine OASL (pOASL) in porcine alveolar macrophages (PAMs) induced by interferon (IFN) -β stimulation and PRRSV infection was examined by real-time polymerase chain reaction (RT-PCR). Exogenous expression and knockdown of pOASL were used to indicate the role of pOASL in the PRRSV replication cycle. The type I IFN signaling pathway was evaluated after pOASL overexpression. Results showed the expression of pOASL in PAMs was significantly increased by IFN-β stimulation or PRRSV infection. pOASL specific small interfering RNA (siRNA) promoted PRRSV replication, whereas exogenous expression of pOASL inhibited infection of PRRSV. The anti-PRRSV activity was lost after knockdown of the Melanoma differentiation-associated protein 5 (MDA5) RNA sensor. Taken together, pOASL inhibits PRRSV infection via the activation of MDA5.