Porcine Reproductive and Respiratory Syndrome Virus Enhances Self-Replication via AP-1–Dependent Induction of SOCS1

Abstract

PRRSV infection induces SOCS1 upregulation. PRRSV N protein upregulates SOCS1, and NLS-2 is essential for this function. AP-1 signaling pathways are indispensable for PRRSV-induced SOCS1 expression. Porcine reproductive and respiratory syndrome virus (PRRSV) has caused tremendous economic losses in the swine industry since its emergence in the late 1980s. PRRSV exploits various strategies to evade immune responses and establish chronic persistent infections. Suppressor of cytokine signaling (SOCS) 1, a member of the SOCS family, is a crucial intracellular negative regulator of innate immunity. In this study, it was shown that SOCS1 can be co-opted by PRRSV to evade host immune responses, facilitating viral replication. It was observed that PRRSV induced SOCS1 production in porcine alveolar macrophages, monkey-derived Marc-145 cells, and porcine-derived CRL2843-CD163 cells. SOCS1 inhibited the expression of IFN-β and IFN-stimulated genes, thereby markedly enhancing PRRSV replication. It was observed that the PRRSV N protein has the ability to upregulate SOCS1 production and that nuclear localization signal–2 (NLS-2) is essential for SOCS1 induction. Moreover, SOCS1 upregulation was dependent on p38/AP-1 and JNK/AP-1 signaling pathways rather than classical type I IFN signaling pathways. In summary, to our knowledge, the findings of this study uncovered the molecular mechanism that underlay SOCS1 induction during PRRSV infection, providing new insights into viral immune evasion and persistent infection.