Viruses transfer the antiviral second messenger cGAMP between cells

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Cyclic GMP-AMP synthase (cGAS) is a key sensor of cytosolic DNA during viral infections.
• cGAS initiates an antiviral state by synthesizing cyclic GMP-AMP (cGAMP), which activates the stimulator of interferon genes (STING) pathway.

Purpose of the Study:

• To investigate the mechanism of cGAMP transfer between cells.
• To explore the potential of cGAMP-loaded viral particles in immunotherapy and vaccine development.

Main Methods:

• Detection of cGAMP incorporation into lentivirus and herpesvirus virions.
• Assessing the transfer of cGAMP to newly infected cells via virions.
• Evaluating STING-dependent antiviral responses triggered by cGAMP-loaded virions.
• Analyzing the activation of dendritic cells upon infection with cGAMP-loaded lentiviruses.

Main Results:

• cGAMP is incorporated into viral particles (lentivirus, herpesvirus) produced in cGAS-expressing cells.
• Transferred cGAMP via virions activates STING-dependent antiviral programs in recipient cells, independent of exosomes or viral nucleic acids.
• cGAMP-loaded lentiviruses enhance dendritic cell activation.

Conclusions:

• Viral particles can serve as a vehicle for transferring innate immune signals (cGAMP) between cells.
• This intercellular cGAMP transfer mechanism can accelerate and broaden antiviral responses.
• Loading viral vectors with cGAMP presents a promising strategy for enhancing vaccine efficacy.