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Coevolution pays off: Herpesviruses have the license to escape the DNA sensing pathway

Abstract

Early detection of viral invasion by pattern recognition receptors (PRR) is crucial for the induction of a rapid and efficient immune response. Cytosolic DNA sensors are the most recently described class of PRR, and induce transcription of type I interferons (IFN) and proinflammatory cytokines via the key adaptor protein stimulator of interferon genes (STING). Herpesviruses are a family of large DNA viruses widely known for their immense arsenal of proteins dedicated to manipulating and evading host immune responses. Tantamount to the significant role played by DNA sensors and STING in innate immune responses, herpesviruses have in turn evolved a range of mechanisms targeting virtually every step of this key signaling pathway. Strikingly, some herpesviruses also take advantage of this pathway to promote their own replication. In this review, we will summarize the current understanding of DNA sensing and subsequent induction of signaling and transcription, and showcase the close adaptation of herpesviruses to their host reflected by the myriad of viral proteins dedicated to modulating this critical innate immune pathway.

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Acknowledgements

This work was supported by the SMART BIOTECS alliance between the Technische Universität Braunschweig and the Leibniz Universität Hannover, funded by the Ministry of Science and Culture (MWK) of Lower Saxony, Germany, and the Deutsche Forschungsgemeinschaft (DFG), BR3432/3-1.

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Correspondence to Melanie M. Brinkmann.

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This article is part of the Special Issue on Immunological Imprinting during Chronic Viral Infection.

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Stempel, M., Chan, B. & Brinkmann, M.M. Coevolution pays off: Herpesviruses have the license to escape the DNA sensing pathway. Med Microbiol Immunol 208, 495–512 (2019). https://doi.org/10.1007/s00430-019-00582-0

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Keywords

  • Pattern recognition receptors
  • cGAS
  • IFI16
  • STING
  • TBK1
  • IRF3
  • NF-κB
  • Type I IFN
  • Herpesvirus
  • Immune evasion
  • HSV-1
  • HSV-2
  • VZV
  • HCMV
  • HHV-6
  • HHV-7
  • EBV
  • KSHV
  • MHV68
  • MCMV
  • Innate immune response
  • Antiviral
  • Modulation