Modulation of host cell responses and evasion strategies for porcine reproductive and respiratory syndrome virus

Abstract

The immune surveillance system protects host cells from viral infection, and viruses have evolved to escape this system for efficient proliferation in the host. Host cells produce cytokines and chemokines in response to viral infection, and among such effector molecules, type I interferons are the principal antiviral cytokines and therefore effective targets for viruses to disarm host surveillance. Porcine reproductive and respiratory syndrome virus (PRRSV) expresses proteins that circumvent the IFN response and other cellular processes, and to compensate the small coding capacity of PRRSV, these proteins are multifunctional. To date, at least four viral proteins have been identified and studied as viral antagonists of host defenses: N as a structural protein and three non-structural proteins, Nsp1 (Nsp1α and Nsp1β), Nsp2, and Nsp11. Among these, N and Nsp1 are nuclear-cytoplasmic proteins distributed in both the nucleus and cytoplasm of cells. Nsp1 and Nsp2 are viral proteases while Nsp11 is an endoribonuclease. This review describes the current understanding of the role of these proteins in modulating the host innate immune responses. Blocking against virus-mediated inhibition of the innate response may lead to the future development of effective vaccines. The understanding of viral mechanisms modulating the normal cellular processes will be a key to the design of an effective control strategy for PRRS.

Carbopol improves the early cellular immune responses induced by the modified-life vaccine Ingelvac PRRS® MLV

“…Th1 responses are associated to increased CD8T cell proliferation (Ekkens et al, 2007), production of opsonizing antibodies (Lefeber et al, 2003) and maximizing macrophage killing activity (Stout et al, 2005), thus providing an optimal milieu for anti-viral immunity. Importantly, the early generation of tissue-tropic effector cells induced by carbopol may counteract the immune escape mechanism evolved by PRRSV such as delayed production of neutralizing antibodies, suppression of interferon type-I IFNs, and up-regulation of IL-10 (Yoo et al, 2010).…”

Carbon Monoxide Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication by the Cyclic GMP/Protein Kinase G and NF-κB Signaling Pathway

“…Unfortunately, neither traditional control strategies nor conventional vaccines achieve consistent PRRS control (4)(5)(6). A major obstacle to successful PRRS vaccine development is the inconsistent induction of protective immunity (7)(8)(9). During PRRSV infection in animals, unknown viral properties apparently allow PRRSV to persist.…”

Differential contributions of porcine bocavirus NP1 protein N- and C-terminal regions to its nuclear localization and immune regulation

“…For optimal survival, some IFN-antagonistic viruses induce the activation of NFk B to facilitate the inflammatory response and the production of immunosuppressive cytokines. For example, PRRSV, a known inhibitor of IFN production that targets the RIG-I (retinoic acid-inducible gene 1) pathway (Luo et al, 2008), has been shown to activate NFk B to induce the production of pro-inflammatory cytokines (IL-6, IL-8 and TNF-a) (Lee & Kleiboeker, 2005;Yoo et al, 2010) and the immunosuppressive cytokine IL-10 ( Song et al, 2013). In this study, we observed that PBoV NP1 induced the activation of NFk B by enhancing phosphorylation of p65 and degradation of IkBa.…”