Progress of cGAS-STING signaling in response to SARS-CoV-2 infection

Abstract

Coronavirus disease 2019 (COVID-19) is an epidemic respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can cause infections in millions of individuals, who can develop lung injury, organ failure, and subsequent death. As the first line of host defense, the innate immune system is involved in initiating the immune response to SARS-CoV-2 infection and the hyperinflammatory phenotype of COVID-19. However, the interplay between SARS-CoV-2 and host innate immunity is not yet well understood. It had become known that the cGAS-STING pathway is involved in the detection of cytosolic DNA, which elicits an innate immune response involving a robust type I interferon response against viral and bacterial infections. Nevertheless, several lines of evidence indicate that SARS-CoV-2, a single-stranded positive-sense RNA virus, triggered the cGAS-STING signaling pathway. Therefore, understanding the molecular and cellular details of cGAS-STING signaling upon SARS-CoV-2 infection is of considerable biomedical importance. In this review, we discuss the role of cGAS-STING signaling in SARS-CoV-2 infection and summarize the potential therapeutics of STING agonists as virus vaccine adjuvants.

Ficolin B secreted by alveolar macrophage exosomes exacerbates bleomycin-induced lung injury via ferroptosis through the cGAS-STING signaling pathway

“…Studies have shown that the cGAS-STING pathway plays an important regulatory role in the regulation of autophagy, ferritinophagy, ferroptosis, and inflammation [ 64 – 67 ]. In addition, studies on alleviating lung injury by inhibiting the activation of the cGAS-STING pathway have been reported, but the literature is relatively few [ 35 – 37 , 68 ]. In this study, by silencing cGAS, it was found that the activation of the cGAS-STING pathway in BLM-induced lung epithelial cells was inhibited, and the levels of autophagy and ferroptosis were also decreased.…”

Age-related influence on DNA damage, proteomic inflammatory markers and oxidative stress in hospitalized COVID-19 patients compared to healthy controls

“…Since oxidative stress markers were not altered in this study, we suggest that DNA damage in COVID-19 patients might be driven by inflammation. Mechanistically, the cGAS-STING pathway plays a pivotal role in the detection of foreign genetic material including viruses such as SARS-Cov-2 [ [68] , [69] , [70] ] and consequently induces immune responses. However, a prolonged activation of this pathway might enhance the risk for chronic inflammation.…”

Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS‐CoV‐2 nucleocapsid protein and its liquid–liquid phase separation

“…114 For example, certain viral proteins have been discovered that obstruct cGAS LLPS, thereby blocking its activation and facilitating immune evasion by the virus. 114 Furthermore, the activation of the DNA sensing protein cGAS and its downstream effector STING can trigger a type-I IFN response in the context of SARS-CoV-2 infection. This implies that cells have the ability to detect SARS-CoV-2 infection and initiate an IFN response, even though the virus can evade certain components of the innate immune system.…”

“…There is substantial evidence to suggest that SARS‐CoV‐2, a single‐stranded positive‐sense RNA virus, instigates the cGAS‐STING signaling pathway. Viruses, SARS‐CoV‐2 among them, have adapted to exploit LLPS for immune evasion 114 . For example, certain viral proteins have been discovered that obstruct cGAS LLPS, thereby blocking its activation and facilitating immune evasion by the virus 114 .…”

“…Viruses, SARS‐CoV‐2 among them, have adapted to exploit LLPS for immune evasion 114 . For example, certain viral proteins have been discovered that obstruct cGAS LLPS, thereby blocking its activation and facilitating immune evasion by the virus 114 . Furthermore, the activation of the DNA sensing protein cGAS and its downstream effector STING can trigger a type‐I IFN response in the context of SARS‐CoV‐2 infection.…”