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Antagonizing interferon-mediated immune response by porcine reproductive and respiratory syndrome virus - PubMed

Review

Antagonizing interferon-mediated immune response by porcine reproductive and respiratory syndrome virus

Rong Wang et al. Biomed Res Int. 2014.

Abstract

Interferons (IFNs) are important components in innate immunity involved in the first line of defense to protect host against viral infection. Porcine reproductive and respiratory syndrome virus (PRRSV) leads to severe economic losses for swine industry since being first identified in early 1990s. PRRSV interplays with host IFN production and IFN-activated signaling, which may contribute to the delayed onset and low level of neutralizing antibodies, as well as weak cell-mediated immune response in infected pigs. PRRSV encodes several proteins that act as antagonists for the IFN signaling. In this review, we summarized the various strategies used by PRRSV to antagonize IFN production and thwart IFN-activated antiviral signaling, as well as the variable interference with IFN-mediated immune response by different PRRSV strains. Thorough understanding of the interaction between PRRSV and host innate immune response will facilitate elucidation of PRRSV pathogenesis and development of a better strategy to control PRRS.

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Figures

**Figure 1**
Interference of type I IFN production by PRRSV proteins. Activation of RLR pathway and signaling by viral dsRNA is shown. Viral dsRNA is generated during PRRSV replication. “P” besides IRF3 and IRF7 indicates phosphorylation. Red-colored blocks indicate PRRSV proteins known to inhibit the signaling molecules indicated. PRRSV nsp1α inhibits IRF3 association with CBP, enhances CBP degradation, and interferes with IκB degradation. And nsp1β inhibits IRF3 phosphorylation and nuclear translocation. Also nsp2 inhibits IRF3 phosphorylation and nuclear translocation, interferes with IκB polyubiquitination, and prevents its degradation. And nsp11 inhibits IRF3 phosphorylation and nuclear translocation via degrading IPS-1 mRNA.

**Figure 2**
Interference with type I IFN-activated JAK/STAT signaling pathway and antiviral ISGs. IFN-α/-β binds to their receptors IFNAR-1 and IFNAR-2 on cell membrane, which activates JAK/STAT pathway. “P” besides STAT1 and STAT2 indicates phosphorylation. PRRSV nsp1β inhibits ISGF3 nuclear translocation via inducing degradation of KPNA1, which is essential for mediating the nuclear import of ISGF3. N protein also inhibits ISGF3 nuclear translocation. And nsp2 reduces ISG15 production and conjugation via its deubiquitination activity.

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Antagonizing interferon-mediated immune response by porcine reproductive and respiratory syndrome virus - PubMed