Innate immune evasion and general host shutoff strategies of human respiratory RNA viruses

To replicate and spread efficiently, RNA viruses must inhibit the host immune signaling pathways and/or induce host shutoff and thereby evade host immunity. However, not all RNA viruses have the same consequences in terms of disease severity and ability to cause reinfections. What are the reasons for such differences? Are there any unique or common features of viral immune evasion? Answering these questions is imperative to elucidate the role of the balance between damaging pro-inflammatory and protective antiviral responses and to inform development of new therapeutic strategies. In this review, we provide a comparative overview of the knowledge regarding the innate immune evasion and general host shutoff strategies used by respiratory RNA viruses to enable their persistent spread in humans. We demonstrate that these viruses encode multiple and often redundant mechanisms of innate immune suppression, with potent general host shutoff being characteristic of viruses with wider host range and greater ability to cause reinfections. Accordingly, we argue that increased research effort in characterizing host shutoff mechanisms of different viruses and their contribution to virus fitness is needed to determine if targeting host shutoff represents a viable avenue for developing new antiviral therapies.