Poly(I:C), a double stranded RNA analog, activates the anti-viral DNA sensors in buffalo fibroblasts

Abstract

Polyinosinic:polycytidylic acid or poly(I:C) is a double stranded RNA analog that is known for stimulating RNA sensing pathways in a variety of cell culture and animal models. Activation of nucleic acid sensing pathways lead to the up-regulation of Interferon-β which ultimately creates an antiviral state in the host. The involvement of intracellular DNA sensors in poly(I:C) mediated immune response has not been extensively explored. Poly(I:C) stimulates the intracellular DNA sensing in addition to RNA sensing pathways in buffalo fibroblasts. Genomic DNA leak into the cytosol due to poly(I:C) is likely to stimulate the intracellular DNA sensing pathways. The mRNA expression of DNA sensors cGAS, IFI16-L (IFI16-like) and DAI are elevated while DDX41 and STING are down-regulated in poly(I:C) treated cells. However, STING activation is evident in poly(I:C) treated cells through the formation of aggregates around the nucleus. IFI16-L also aggregates like STING and translocates from the nucleus to the cytoplasm in response to poly(I:C). The activation of DNA sensors by a dsRNA mimic indicates that mammalian cells can use their own molecules for defending themselves against pathogenic RNA viruses. This provides an opportunity to search for novel therapeutic targets against RNA viruses that evade detection by canonical pattern recognition receptors.