Abstract
Interferons (IFNs) are a family of cytokines that play a pivotal role in orchestrating the innate immune response during viral infections, thus representing the first line of defense in the host. After binding to their respective receptors, they are able to elicit a plethora of biological activities, by initiating signaling cascades which lead to the transcription of genes involved in antiviral, anti-inflammatory, immunomodulatory and antitumoral effector mechanisms. In hindsight, it is not surprising that viruses have evolved multiple IFN escape strategies toward efficient replication in the host. Hence, in order to achieve insight into preventive and treatment strategies, it is essential to explore the mechanisms underlying the IFN response to viral infections and the constraints thereof. Accordingly, this review is focused on three RNA and three DNA viruses of major importance in the swine farming sector, aiming to provide essential data as to how the IFN system modulates the antiviral immune response, and is affected by diverse, virus-driven, immune escape mechanisms.
Highlights
Interferons (IFNs) are a family of cytokines that elicit pleiotropic biological effects and can be synthesized and secreted by most cell types
IFN-λ3 can significantly reduce the replication of PRRSV in porcine alveolar macrophages (PAMs), and such inhibition is dose- and time-dependent; plaque formation can be abrogated entirely, and virus yield is dramatically reduced when PAMs are treated with IFN-λ3 at 1000 ng/mL; these effects are in agreement with the expression of interferon-stimulated genes 15 (ISG15), 2’-5’oligoadenylate synthase 1 (OAS1), IFN-inducible transmembrane 3 (IFITM3) and myxoma resistance protein 1(Mx1) in primary PAMs [42]
Potent (250–300 PD50 ) Foot-and-Mouth disease (FMD) vaccines developed in the Russian Federation were reported to confer protection in cattle as early as 1 day after injection, the protective effects being highest after vaccine administration in the mucous membranes of upper lips; the authors provided evidence of Foot-and-Mouth Disease Virus (FMDV) receptor blockage in vitro, the involvement of an innate immune response is more credible in vivo to account for early protection [86]
Summary
Interferons (IFNs) are a family of cytokines that elicit pleiotropic biological effects and can be synthesized and secreted by most cell types These proteins are characterized by antiviral activity, discovered in 1957 by Isaacs and Lindenmann [1] during studies on virus interference. These transcription factors, once phosphorylated, are translocated to the nucleus and initiate the transcription of NF-κB and IRF3 [15,16] By binding to their respective receptors, type I IFNs (α/β) are able to activate, through a JAK/STAT-mediated pathway, the transcription of several interferon stimulated genes (ISGs) which encode for several innate immune effectors [17]. STATs complexes translocate into the nucleus, where they bind IFN-stimulated response elements (ISRE) or gamma-activated sequences (GAS) This determines the transcription of hundreds of genes involved in antiviral response, including. We focus on the IFN response modulated by three RNA and three DNA viruses, sustaining diseases associated to severe morbidity and heavy economic losses in swine farms
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