Activation of cGAS-dependent antiviral responses by DNA intercalating agents

作者：Pepin Genevieve; Nejad Charlotte; Thomas Belinda J; Ferrand Jonathan; McArthur Kate; Bardin Philip G; Williams Bryan R G; Gantier Michael P

来源：Nucleic Acids Research, 2017, 45(1): 198-205.

DOI：10.1093/nar/gkw878

Acridine dyes, including proflavine and acriflavine, were commonly used as antiseptics before the advent of penicillins in the mid-1940s. While their mode of action on pathogens was originally attributed to their DNA intercalating activity, work in the early 1970s suggested involvement of the host immune responses, characterized by induction of interferon (IFN)-like activities through an unknown mechanism. We demonstrate here that sub-toxic concentrations of a mixture of acriflavine and proflavine instigate a cyclic-GMP-AMP (cGAMP) synthase (cGAS)dependent type-I IFN antiviral response. This pertains to the capacity of these compounds to induce low level DNA damage and cytoplasmic DNA leakage, resulting in cGAS-dependent cGAMP-like activity. Critically, acriflavine: proflavine pre-treatment of human primary bronchial epithelial cells significantly reduced rhinovirus infection. Collectively, our findings constitute the first evidence that non-toxic DNA binding agents have the capacity to act as indirect agonists of cGAS, to exert potent antiviral effects in mammalian cells.

• 出版日期2017-1
• 单位河北医科大学