Camouflage and interception: How pathogens evade detection by intracellular nucleic acid sensors.

Intracellular DNA and RNA sensors play a vital part in the innate immune response to viruses and other intracellular pathogens, causing the secretion of type I interferons, cytokines and chemokines from infected cells. Pathogen RNA can be detected by RIG-I-like receptors in the cytosol, while cytosolic DNA is recognised by DNA sensors such as cyclic GMP-AMP synthase (cGAS). The resulting local immune response, which is initiated within hours of infection, is able to eliminate many pathogens before they are able to establish an infection in the host. For this reason, all viruses, and some intracellular bacteria and protozoa, need to evade detection by nucleic acid sensors. Immune evasion strategies include the sequestration and modification of nucleic acids, and the inhibition or degradation of host factors involved in innate immune signalling. Large DNA viruses, such as herpesviruses, often use multiple viral proteins to inhibit signalling cascades at several different points; for instance Herpes Simplex Virus 1 (HSV-1) targets both DNA sensors cGAS and IFI16, as well as the adaptor protein STING and other signalling factors in the pathway. Viruses with a small genome enocde only few immunomodulatory proteins, but these are often multifunctional, such as the NS1 protein from Influenza A virus which inhibits RNA sensing in multiple ways. Intracellular bacteria and protozoa can also be detected by nucleic acid sensors. However, as the type I interferon response is not always beneficial for the host under these circumstances, some bacteria subvert, rather than evade, these signalling cascades for their own gain. This article is protected by copyright. All rights reserved.