Abstract
The immune system protects the organism against infections and the damage associated with them. The first line of defense against pathogens is the innate immune response. In the case of a viral infection, it induces the interferon (IFN) signaling cascade and eventually the expression of type I IFN, which then causes an antiviral state in the cells. However, many viruses have developed strategies to counteract this mechanism and prevent the production of IFN. In order to modulate or inhibit the IFN signaling cascade in their favor, viruses have found ways to interfere at every single step of the cascade, for example, by inducing protein degradation or cleavage, or by mediate protein polyubiquitination. In this article, we will review examples of viruses that modulate the IFN response and describe the mechanisms they use.
Highlights
The mammalian immune system evolved to detect and fight viral infections effectively
There are recent articles that review how viruses prevent detection by pathogen recognition receptors (PRRs) [13, 14] and how viruses modulate innate immune signaling by use of viral deubiquitinases [15]
When a recent study tested how the rabies virus P protein of street strains behaves compared to laboratory-adapted strains with regard to the induction of type I IFN, they found that both street strains and laboratory strains inhibit TANK-binding kinase 1 (TBK1)-mediated signaling, but only the P protein of street strains interacts with and inhibits IKKε-inducible IRF3dependent IFNβ expression [88] (Figure 1)
Summary
The immune system protects the organism against infections and the damage associated with them. The first line of defense against pathogens is the innate immune response. In the case of a viral infection, it induces the interferon (IFN) signaling cascade and eventually the expression of type I IFN, which causes an antiviral state in the cells. Many viruses have developed strategies to counteract this mechanism and prevent the production of IFN. In order to modulate or inhibit the IFN signaling cascade in their favor, viruses have found ways to interfere at every single step of the cascade, for example, by inducing protein degradation or cleavage, or by mediate protein polyubiquitination. We will review examples of viruses that modulate the IFN response and describe the mechanisms they use
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