Viral Innate Immune Evasion and the Pathogenesis of Emerging RNA Virus Infections

Abstract

Positive-sense single-stranded RNA (+ssRNA) viruses comprise many (re-)emerging human pathogens that pose a public health problem. Our innate immune system and in particular the interferon response form the important first line of defense against these viruses. Given their genetic flexibility, these viruses have therefore developed multiple strategies to evade the innate immune response in order to optimize their replication capacity. Already many molecular mechanisms of innate immune evasion by +ssRNA viruses have been identified. However, research addressing the effect of host innate immune evasion on the pathology caused by the viral infection is less prevalent in literature, though very relevant and interesting. Since interferons have been implicated in inflammatory diseases and immunopathology in addition to their protective role in infection, the influence of antagonizing the immune response may have an ambiguous effect on the clinical outcome of the viral disease. Therefore, this review discusses what is currently known about the role of interferons and host immune evasion in the pathogenesis of emerging viruses belonging to the coronaviruses, alphaviruses and flaviviruses.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response

“…Other studies have concluded that this therapy does not have a beneficial effect on patients [38,42].…”

“…DUB is another role of PLpro to help coronavirus evade attack from a host's immune response by antagonizing the IFN response. From these findings, we hypothesized that the decline in function of the two proteins may lead to the direct introduction and sticking of immune troops to continuously infected cells and prevented the replication of the virus and the life cycle [37,38]. In addition to using nonstructural proteins, SARS-CoV could utilize its protein accessories to avoid immune responses.…”

Coronavirus infections and immune responses

“…When a virus invades the host, PRRs initially recognize the viral nucleic acid, collect the specific signal adapter protein, activate IRF3 and IRF7 before being translocated to the nucleus and promote the synthesis of type I interferons (IFNs). Type I IFNs subsequently activate the downstream JAK‐STAT signal pathway, promote the expression of IFN‐stimulated genes (ISGs) 37,38 …”

COVID‐19: A Global Threat to the Nervous System

“…SARS-CoV has developed multiple strategies to evade the innate immune response in order to optimize its replication capacity. 61 It seems likely that SARS-CoV-2 uses the same strategy. The magnitude of the immune response against SARS-CoV-2 needs to be precisely calibrated to control viral replication without triggering immunopathogenic injury.…”