Origin and function of anti-interferon type I viral proteins

Type I interferons (IFN-I) are the most important innate immune cytokines produced by vertebrate host cells following, virus infection. Broadly speaking, detection of infecting viral nucleic acids by pattern recognition receptors (PRR) and subsequent downstream signaling triggers synthesis of a large number of IFN-I-stimulated genes (ISGs), endowed with diverse antiviral effector function. The co-evolution of virus-host interactions over million years has resulted in the emergence of viral strategies that target and inhibit host PRR-mediated detection, signal transduction pathways and IFN-I-mediated stimulation of ISGs. In this review, we illustrate the multiple mechanisms of viral immune evasion and discuss the co-evolution of anti-IFN-I viral proteins by summarizing key examples from recent literature. Due to the large number of anti-IFN-I proteins described, we provide here an evaluation of the prominent examples from different virus families. Understanding the unrelenting evolution of viral evasion strategies will provide mechanistic detail concerning these evolving interactions but will further enhance the development of tailored antiviral approaches. Evolutionary path leading to anti-IFN-I viral gene appearance resulting in several anti IFN-I system viral proteins acting with diverse mechanisms. • IFN-I system is critically important for host protection against virus invasion. • Viruses' genomes express proteins endowed with anti IFN-I-based responses. • Co-evolution took place between anti-IFN-I viral proteins and their hosts. • New antivirals can be discovered knowing anti-IFN-I proteins mechanisms of action.