Interplay between Interferon-Mediated Innate Immunity and Porcine Reproductive and Respiratory Syndrome Virus

Abstract

Innate immunity is the first line of defense against viral infection, and in turn, viruses have evolved to evade host immune surveillance. As a result, viruses may persist in host and develop chronic infections. Type I interferons (IFN-α/β) are among the most potent antiviral cytokines triggered by viral infections. Porcine reproductive and respiratory syndrome (PRRS) is a disease of pigs that is characterized by negligible induction of type I IFNs and viral persistence for an extended period. For IFN production, RIG-I/MDA5 and JAK-STAT pathways are two major signaling pathways, and recent studies indicate that PRRS virus is armed to modulate type I IFN responses during infection. This review describes the viral strategies for modulation of type I IFN responses. At least three non–structural proteins (Nsp1, Nsp2, and Nsp11) and a structural protein (N nucleocapsid protein) have been identified and characterized to play roles in the IFN suppression and NF-κB pathways. Nsp’s are early proteins while N is a late protein, suggesting that additional signaling pathways may be involved in addition to the IFN pathway. The understanding of molecular bases for virus-mediated modulation of host innate immune signaling will help us design new generation vaccines and control PRRS.

Inhibition of interferon gene activation by death-effector domain-containing proteins from the molluscum contagiosum virus

“…However, the overexpression of MC159, or any other FLIP, did not induce IFN-β enhancer activity in both cell types tested here. The porcine reproductive and respiratory syndrome virus (PRRSV) nsp11 protein is a known inhibitor of IFN-β activation via its ability to inhibit IRF3 and NF-κB (49,50). As would be expected, luciferase activity was low in nsp11-expressing cells and was used as a positive control.…”

“…TBK1 protein levels were diminished in cells coexpressing nsp11. Nsp11 possesses endoribonuclease activity and is known to target MAVS (49,50). While nsp11 has not been reported to degrade TBK1 mRNA, it would be reasonable to predict that nsp11 could target other cellular mRNAs.…”

“…2C), suggesting that each MCV protein inhibited an event upstream of IRF3 activation. Nsp11 overexpression also did not inhibit constitutively active IRF3, which was expected given that nsp11 is thought to act as an endoribonuclease to target the degradation of MAVS transcripts (49,50). Viral protein level expression was verified by immunoblotting to ensure that the lack of inhibition was not due to a lack of protein expression.…”

MicroRNA-30c Modulates Type I IFN Responses To Facilitate Porcine Reproductive and Respiratory Syndrome Virus Infection by Targeting JAK1

“…PRRSV infection induces poor IFN-I responses, and several PRRSV proteins, including Nsp1, Nsp2, Nsp11, N protein (29,30), and Nsp4 (36,42), were shown to antagonize IFNs. Nsp1 was identified as the most potent antagonist and is able to inhibit the production and signaling of IFN-I.…”

“…The etiological agent of the disease is porcine reproductive and respiratory syndrome virus (PRRSV), an enveloped positive-strand RNA virus that belongs to the Arteriviridae family (28). During PRRSV infection, IFN-I production and signaling are severely crippled (29,30). Recently, several reports showed that many miRNAs are altered by PRRSV, raising the possibility that they are involved in its pathogenesis (31,32).…”