Table 3.

Herpesvirus proteins that regulate DNA sensing and DNA activated signaling pathway.

	PRR	Virus	Viral protein	Experimental system	Proposed Mechanism	References
Inhibition of DNA sensing	IFI16	HSV-1	ICP0	human foreskin fibroblasts (HFF)	Promotes the 7 degradation of IFI16	Orzalli et al., 2012
			UL41	HFF, Hela	Degrades the IFI16 mRNA	Orzalli et al., 2016
		HCMV	pUL83	HFF, human embryo kidney (HEK) 293T cell	Interacts with the IFI16 pyrin domain and blocks its oligomerization upon DNA sensing	Li T. et al., 2013
			pUL97	HELFs, HEK 293 cells	Binds to IFI16 and relocalizes it to the cytoplasm	Dell’oste et al., 2014
		KSHV	Lytic Proteins	BCBL-1 and BJAB cells	Promotes the ubiquitination and proteasomal degradation of IFI16	Roy et al., 2016
	cGAS	HSV-1	UL37	human monocyte THP-1 cells	Deamidates human and mouse cGAS	Zhang et al., 2018
			UL41	HEK293T	Selectively degrades cGAS mRNA	Su and Zheng, 2017
			VP22	HEK293T, Hela	Interacts with cGAS	Huang J. et al., 2018
		HCMV	UL31	HEK293T	Interacts with cGAS and disassociates DNA from cGAS	Huang Z. F. et al., 2018b
			pUL83	HFF, HEK 293	Binds to cGAS and inhibits its enzymatic activity	Biolatti et al., 2018
		KSHV	LANA	BCBL-1 PEL cell	Binds to cGAS	Zhang et al., 2016
			ORF52	In Vitro enzymatic assay, HEK293T–STING cells	Interacts with cGAS and DNA	Wu et al., 2015
		EBV	ORF52
	AIM2	HSV-1	VP22	293FT cells, mouse macrophage cell line	Interacts with AIM2 and prevents its oligomerization	Maruzuru et al., 2018
			pUL83	HEK293T, macrophages	Interacts with AIM2 and inhibits activation of AIM2 inflammasome	Huang et al., 2017b
	DNA-pK	HSV-1	ICP0	HeLa S3 cells	Degrades the catalytic subunit of DNA-PK	Parkinson et al., 1999
		EBV	LMP1	nasopharyngeal carcinoma (NPC) cell line	Inhibits DNA-PK phosphorylation and activity	Lu et al., 2016
Inhibition of DNA activated signaling pathway	STING	HSV-1	ICP0	in HEp-2 cells	Stabilizes STING in HEp-2 cells, that is necessary for optimal HSV-1 replication	Kalamvoki and Roizman, 2014
			ICP27	THP 1 cells	Interacts with TBK1 and STING	Christensen et al., 2016
			UL46	HEK293T cells	Interacts with STING and TBK1	Deschamps and Kalamvoki, 2017; You et al., 2019
			γ134.5	HFF	Binds to STING and perturbs its trafficking	Pan et al., 2018
		HCMV	UL42	HFF cell, HEK293T STING cell	Interacts with both cGAS and STING, inhibits cGAS-DNA interaction, oligomerization and enzymatic activity of cGAS. Impairs translocation of STING from the ER to perinuclear punctate structures.	Fu et al., 2019
			UL82	HFF	Interacts with and STING and inhibits its translocation from the ER to perinuclear microsomes	Fu et al., 2017
			pUL48	HFF	Deubiquitinase STING	Kumari et al., 2017
		KSHV	vIRF1	HEK293T STING cell	Prevents the phosphorylation and activation of STING by disrupting STING -TBK1 interaction	Ma et al., 2015