Thursday 27. June 2019

STING induces early IFN-β in the liver and constrains myeloid cell-mediated dissemination of murine cytomegalovirus

Pia Tegtmeyer

Key Message

Primary infections with human cytomegalovirus (HCMV) are usually asymptomatic; however, the host response cannot eliminate the virus. Instead, the virus establishes a latent infection and resides in cells of the body lifelong. Under conditions of immunosuppression latent HCMV can reactivate and cause severe disease that may even lead to death. How the primary infection is sensed by cells of the innate immune system and whether the involved sensing platforms also control viral dissemination within the body was largely unclear. Therefore, we performed experiments in the mouse model. Our results indicate that signaling of the three main recognition platforms, Toll-like receptors, RIG-I like receptors and the cGAS/STING axis, act together to sense primary murine cytomegalovirus (MCMV) infection and induce protective immunity. Interestingly, also under in vivo conditions the cGAS/STING axis is particularly important to constrain MCMV replication in myeloid cells, whereas it is not restricting MCMV dissemination from the liver to other target organs. 

Translational perspective

Understanding the mechanism of how primary CMV infection is sensed and how viral dissemination is regulated can unveil new therapeutic targets that will help to prevent or to better treat CMV infection.