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

Abstract

Summary 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 retinoic‐acid inducible gene I‐like receptors in the cytosol, whereas cytosolic DNA is recognized 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 targets both DNA sensors cGAS and interferon‐γ‐inducible protein 16, as well as the adaptor protein STING (stimulator of interferon genes) and other signalling factors in the pathway. Viruses with a small genome encode only a 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.

Exploring active ingredients and function mechanisms of Ephedra-bitter almond for prevention and treatment of Corona virus disease 2019 (COVID-19) based on network pharmacology

“…However, as the virus continues to mutate, the body sometimes cannot respond as quickly as needed. At this time, the intervention of drugs or vaccines may increase the body’s sensitivity to viral stimulation, thereby restoring the balance of the immune ecosystem in the infected host tissue [ 62 ]. As shown by the results of the GO analysis in this study, ephedra-bitter almond may participate in biological processes such as immune regulation by enhancing the body’s response to pathogen stimulation.…”

The HSV-1 ubiquitin ligase ICP0: Modifying the cellular proteome to promote infection

“…Detection of viral nucleic acid by host pattern recognition receptors (PRRs) plays a critical role in the activation of signalling cascades that lead to the production of pro-inflammatory cytokines, including type-I, II, and III IFNs ( Unterholzner and Almine, 2019 ; Stempel et al, 2019 ; Alandijany, 2019 ). Secretion of IFNs leads to the induction of hundreds of IFN stimulated genes (ISGs) that generate a cellular antiviral state that limits virus propagation and spread.…”

IL-36 promotes anti-viral immunity by boosting sensitivity to IFN-α/β in IRF1 dependent and independent manners

“…Thus, in the present model system, while HSV-1 actively diminish the amount of type I IFN produced by infected keratinocytes 16 , the cells mount the same immune response due to their higher levels of IFNAR induced by IL-36. Active antagonism of IFN production is common among viruses, many of which replicate in epithelial cells 26 . Our identified pathway involving IL-36 enhancement of IFN responses represent a first line of defense to counteract these immune evasion strategies.…”