Evasion of Host Innate Immunity by Emerging Viruses: Antagonizing Host RIG-I Pathways

Viruses confront a seemingly dichotomous relationship with their host cells. They must overcome host defenses in order to complete their infectious cycles and generate new viruses yet the host must remain healthy and hospitable for that to take place. Shortly after infection, the RIGI-like receptors (RLRs) within the cytoplasm of the infected cell recognize foreign motifs present in the pathogen. The host responds by activating a signaling pathway that leads to activation of cellular transcription factors, including the NF-κB and interferon regulatory factor 3 (IRF3), that are necessary for induction of the type 1 interferon genes. Many viruses subdue components of the host innate immune system to facilitate viral replication. Viruses with single stranded RNA genomes that possess double stranded replication intermediates, 5' triphosphates or 5' diphosphates along with other secondary recognition motifs including length express proteins that either hide their dsRNA from detection by RLRs, interact with RIG-I directly, or interfere with components of the RIG-I pathway with the ultimate goal of evading innate immunity. In every case the end result is that the host antiviral defense system is crippled and viral propagation can proceed. In this review we focus on the eight emerging viruses most likely to cause major epidemics, including Arenaviruses, Bunyaviruses, Coronaviruses, Filoviruses and Paramyxoviruses, as identified by the World Health Organization in 2016. Once fully understood, the mechanisms employed by viruses to evade host cell immunity may serve as effective targets for a variety of antiviral agents.