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Review
. 2021 Mar 15:11:647992.
doi: 10.3389/fcimb.2021.647992. eCollection 2021.

Evasion of Intracellular DNA Sensing by Human Herpesviruses

Debipreeta Bhowmik  1 , Fanxiu Zhu  1
Affiliations
Review

Evasion of Intracellular DNA Sensing by Human Herpesviruses

Debipreeta Bhowmik et al. Front Cell Infect Microbiol. .

Abstract

Sensing of viral constituents is the first and critical step in the host innate immune defense against viruses. In mammalian cells, there are a variety of pathogen recognition receptors (PRRs) that detect diverse pathogen-associated molecular patterns (PAMPs) including viral RNA and DNA. In the past decade, a number of host DNA sensors have been discovered and the underlying sensing mechanisms have been elucidated. Herpesviruses belong to a large family of enveloped DNA viruses. They are successful pathogens whose elaborate immune evasion mechanisms contribute to high prevalence of infection among their hosts. The three subfamilies of herpesviruses have all been found to employ diverse and overlapping strategies to interfere with host DNA sensing. These strategies include masking viral DNA or the DNA sensor, degradation of the DNA sensor, and post-transcriptional modification of the DNA sensor or its adaptor protein. In this review, we will discuss the current state of our knowledge on how human herpesviruses use these strategies to evade DNA-induced immune responses. Comprehensive understanding of herpesvirus immune-evasion mechanisms will aid in the development of vaccines and antivirals for herpesvirus-associated diseases.

Keywords: DNA sensing; cGAS; herpesvirus; innate immune response; viral evasion.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Intracellular sensing of herpesvirus DNA by DNA sensors and activation of signaling pathway. CpG DNA in the endosome is sensed by TLR9, leading to the production of type I interferon. AIM2 and IFI16 detect DNA in the cytoplasm and nucleus respectively and activate inflammasome pathway. Detection of DNA by cGAS activates STING signaling, resulting in the induction of type I interferon.
Figure 2
Figure 2
Modulation of DNA Sensing pathways by herpesvirus. Multiple steps in the signaling pathway are targeted by herpesvirus encoded proteins. Red solid line indicates inhibition of a particular pathway by the respective herpesvirus protein.
See this image and copyright information in PMC

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