Abstract

The innate immune response is initiated by the interaction of stereotypical pathogen components with genetically conserved receptors for extracytosolic pathogen-associated molecular patterns (PAMPs) or intracytosolic nucleic acids. In multicellular organisms, this interaction typically clusters signal transduction molecules and leads to their activations, thereby initiating signals that activate innate immune effector mechanisms to protect the host. In some cases programmed cell death—a fundamental form of innate immunity—is initiated in response to genotoxic or biochemical stress that is associated with viral infection. In this paper we will summarize innate immune mechanisms that are relevant to viral pathogenesis and outline the continuing evolution of viral mechanisms that suppress the innate immunity in mammalian hosts. These mechanisms of viral innate immune evasion provide significant insight into the pathways of the antiviral innate immune response of many organisms. Examples of relevant mammalian innate immune defenses host defenses include signaling to interferon and cytokine response pathways as well as signaling to the inflammasome. Understanding which viral innate immune evasion mechanisms are linked to pathogenesis may translate into therapies and vaccines that are truly effective in eliminating the morbidity and mortality associated with viral infections in individuals.

Highlights

  • The innate immune system is as ancient as the bacterial immune response to bacteriophages

  • In this paper we will summarize findings in the innate immune system that are relevant to viral pathogenesis and outline the evolution of viral mechanisms that suppress innate immunity in mammalian hosts

  • mitochondrial antiviral signaling protein (MAVS) induces IKKα and IKKβ stimulation that leads to translocation of NF-κB, as well as IKKε/TBK1 stimulation that leads to translocation of IRF-3

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Summary

Introduction

The innate immune system is as ancient as the bacterial immune response to bacteriophages. As the nature and complexity of viral innate immune evasion mechanisms evolved, so has the innate—and eventually adaptive— immune response to these mechanisms. Signal transduction pathways are stimulated in sentinel cells, such as macrophages and dendritic cells. Stimulation of these signaling pathways promptly activates innate effector mechanisms to protect the host; these innate immune signals activate antigen-presenting cells that are critical to the eventual adaptive immune response of the host [1]. In this paper we will summarize findings in the innate immune system that are relevant to viral pathogenesis and outline the evolution of viral mechanisms that suppress innate immunity in mammalian hosts

The Innate Immune System
Evolution of the Antiviral Innate Immune Response
Viral Evasion of Host Defenses
A46 TIR adapter IRAKs
Conclusion

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