Polyinosinic:polycytidylic acid explained

Polyinosinic:polycytidylic acid (usually abbreviated poly I:C or poly(I:C)) is an immunostimulant. It is used in the form of its sodium salt to simulate viral infections.^[1]

Poly I:C is known to interact with toll-like receptor 3 (TLR3), which is expressed at the endosomal membrane of B-cells, macrophages and dendritic cells. Poly I:C is structurally similar to double-stranded RNA, which is present in some viruses and is a "natural" stimulant of TLR3. Thus, Poly I:C can be considered a synthetic analog of double-stranded RNA and is a common tool for scientific research on the immune system.^[2]

Poly I:C has been shown to activate schizophrenia-like behavior in the offspring of pregnant mice, which can be accompanied by decreased GABAergic transmission in the dentate gyrus.^[3]

Chemistry

Poly I:C is a mismatched double-stranded RNA with one strand being a polymer of inosinic acid, the other a polymer of cytidylic acid.

Variants

Optimization of physicochemical properties of poly I:C has led to generation of derivatives that have increased stability in body fluids (such as polyICLC), or reduced toxicity through reduced stability in body fluids (such as poly I:C₁₂U).^[4]

Notes and References

1. Fortier ME, Kent S, Ashdown H, Poole S, Boksa P, Luheshi GN . The viral mimic, polyinosinic:polycytidylic acid, induces fever in rats via an interleukin-1-dependent mechanism . American Journal of Physiology. Regulatory, Integrative and Comparative Physiology . 287 . 4 . R759–R766 . October 2004 . 15205185 . 10.1152/ajpregu.00293.2004 . 24028101 .
2. Li Y, Xu XL, Zhao D, Pan LN, Huang CW, Guo LJ, Lu Q, Wang J . TLR3 ligand Poly IC Attenuates Reactive Astrogliosis and Improves Recovery of Rats after Focal Cerebral Ischemia . CNS Neuroscience & Therapeutics . 21 . 11 . 905–913 . November 2015 . 26494128 . 4638223 . 10.1111/cns.12469 .
3. Xia Y, Zhang Z, Lin W, Yan J, Zhu C, Yin D, He S, Su Y, Xu N, Caldwell RW, Yao L, Chen Y . Modulating microglia activation prevents maternal immune activation induced schizophrenia-relevant behavior phenotypes via arginase 1 in the dentate gyrus . Neuropsychopharmacology . 45 . 11 . 1896–1908 . October 2020 . 32599605 . 7608378 . 10.1038/s41386-020-0743-7 .
4. Naumann K, Wehner R, Schwarze A, Petzold C, Schmitz M, Rohayem J . Activation of dendritic cells by the novel Toll-like receptor 3 agonist RGC100 . Clinical & Developmental Immunology . 2013 . 283649 . 2013-12-02 . 24454470 . 3878805 . 10.1155/2013/283649 . free .