Regulating STING in health and disease

Journal of Inflammation

Table 3 STING-mediated evasion of antiviral immunity

Pathogen	Mechanism of Action	References
Yellow fever virus Dengue virus	NS4B interrupts STING activation	[11]
Hepatitis C virus	NS3/4A, NS4B proteases interrupt STING activation	[137, 138]
Herpes simplex virus-1	Release ICP0 E3 ubiquitin ligase to degrade IFI16 Viral protein ICP27 binds to STING-TBK1 complex to prevent IRF3 signalling	[139, 140, 147]
Coronaviruses SARS and NL63	Disrupt K63-linked ubiquitin-mediated STING dimerisation	[140]
Human papillomavirus	E2 protein inhibits STING transcription E7 oncogene blocks cGAS/STING signalling	[141, 142]
Adenovirus	E1A oncogene blocks cGAS/STING signalling	[142]
Hepatitis B virus	Disrupts K63-linked ubiquitin-mediated STING dimerisation	[143]
Kaposi’s sarcoma-associated herpesvirus	ORF52 proteins bind to and inhibit cGAS Targets IFI16 degradation during lytic reactivation	[62]
Epstein-Barr virus, Murine gammaherpesvirus 68, Rhesus monkey rhadinovirus	ORF52 proteins bind to and inhibit cGAS	[144, 145]
Human immunodeficiency virus	Enhance STING suppressor NLRX1 Enhance TREX1 to degrade excessive cDNA Viral Capsids prevent innate sensing of cDNA	[67, 65, 68, 146, 148]
Human cytomegalovirus	Tegument protein pUL83 disrupts IFI16 oligomerization and activation	[63]

A number of DNA and RNA viruses have been found to encode and secrete STING-targeted proteases or inhibitors to prevent innate immune detection to help establish the of latent phase of infection. Viruses of the same family tend to adopt similar strategies/mechanisms to block STING activation. Some viruses also express multiple inhibitors to target both DNA sensors and STING, or release viral oncogenes in parallel to further compromise immunity, which consequently increases their chance of survival in the host

ISSN: 1476-9255