Poly(I:C) inhibits porcine reproductive and respiratory syndrome virus replication in MARC-145 cells via activation of IFIT3

• Poly(I:C) inhibited PRRSV replication in MARC-145 cells, following the appearance of increased IFIT3.
• IFIT3 level correlated with the resistance of the cells to PRRSV replication.
• IFIT3 level affected positively the IFN-β promoter activity induced by poly(I:C).
• IFIT3–TBK1–pIRF3 axis was activated in the cells after poly(I:C) treatment.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major cause of heavy economic losses in many swine-producing regions. Current vaccination strategies and antiviral drugs provide only limited protection. Interferon (IFN)-induced protein with tetratricopeptide repeats 3 (IFIT3) has been characterized as the product of a novel antiviral gene and as an important modulator in innate immunity. However, the role of IFIT3 in PRRSV infection is scarcely understood. In this study, polyinosinic–polycytidylic acid (poly(I:C)) inhibited PRRSV replication in MARC-145 cells, following the appearance of increased IFIT3. Overexpression of porcine IFIT3 resulted in a decrease of PRRSV. Knockdown of IFIT3 in MARC-145 cells increased PRRSV replication and impaired the antiviral activity mediated by poly(I:C). Moreover, in the presence or absence of IFIT3, poly(I:C)-induced IFN-β promoter activity was significantly boosted or crippled, respectively. IFIT3, TBK1 and phosphorylation of IRF3 were activated in poly(I:C)-transfected MARC-145 cells. It demonstrated that IFIT3 plays an important role in IFN-β induction in MARC-145 cells, and, when activated, it can inhibit PRRSV replication.