Insights on the cGAS-STING Signaling Pathway During Herpesvirus Infections

Abstract

Herpesviruses belong to large double-stranded DNA viruses. They are under a wide range of hosts and establish lifelong infection, which creates a burden on human health and animal health. Innate immunity is the host's innate defense ability. Activating the innate immune signaling pathway and producing type I interferon is the host's first line of defense against infectious pathogens. Emerging evidence indicates that the cGAS-STING signaling pathway plays an important role in the innate immunity in response to herpesvirus infections. In parallel, because of the constant selective pressure imposed by host immunity, herpesvirus also evolves to target the cGAS-STING signaling pathway to inhibit or escape the innate immune responses. In the current review, we insight on the classical cGAS-STING signaling pathway. We describe the activation of cGAS-STING signaling pathway during herpesvirus infections and strategies of herpesvirus targeting this pathway to evade host antiviral response. Furthermore, we outline the immunotherapy boosting cGAS-STING signaling pathway.

Keywords: antiviral response; cGAS-STING signaling pathway; herpesvirus; immunotherapy; innate immune; viral evasion.

Figure 1

The classical cGAS-STING signaling pathway. The green arrows indicate the activation of this pathway and induction of the IFN-I response. The yellow arrow indicates the synthesis of cGAMP. The blue arrow indicates the phosphorylation of IRF3. Protein phosphorylation is depicted as P. The question mark indicates that the specific mechanism has not been elucidated.

Figure 2

Strategies of cGAS-STING signaling pathway activation and virus evasion during herpesvirus infections. Black letters represent herpesviruses. Red letters indicate the proteins of these viruses. Green letters indicate cellular proteins that favor cGAS-STING signaling pathway activation.