Invertebrate Iridescent Virus 6, a DNA Virus, Stimulates a Mammalian Innate Immune Response through RIG-I-Like Receptors

被引:28
作者
Ahlers, Laura R. H. [1 ,2 ]
Bastos, Reginaldo G. [1 ]
Hiroyasu, Aoi [1 ]
Goodman, Alan G. [1 ]
机构
[1] Washington State Univ, Coll Vet Med, Sch Mol Biosci, Pullman, WA 99164 USA
[2] Washington State Univ, NIH Prot Biotechnol Grad Training Program, Pullman, WA 99164 USA
基金
美国国家卫生研究院;
关键词
NF-KAPPA-B; DOUBLE-STRANDED-RNA; VESICULAR STOMATITIS-VIRUS; CYCLIC GMP-AMP; ANTIVIRAL IMMUNITY; ENDOPLASMIC-RETICULUM; GROWTH ARREST; CYTOSOLIC DNA; INTERFERON; HELICASE;
D O I
10.1371/journal.pone.0166088
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Insects are not only major vectors of mammalian viruses, but are also host to insect-restricted viruses that can potentially be transmitted to mammals. While mammalian innate immune responses to arboviruses are well studied, less is known about how mammalian cells respond to viruses that are restricted to infect only invertebrates. Here we demonstrate that IIV-6, a DNA virus of the family Iridoviridae, is able to induce a type I interferondependent antiviral immune response in mammalian cells. Although IIV-6 is a DNA virus, we demonstrate that the immune response activated during IIV-6 infection is mediated by the RIG-I-like receptor 9RLR) pathway, and not the canonical DNA sensing pathway via cGAS/STING. We further show that RNA polymerase III is required for maximal IFN-beta secretion, suggesting that viral DNA is transcribed by this enzyme into an RNA species capable of activating the RLR pathway. Finally, we demonstrate that the RLR-driven mammalian innate immune response to IIV-6 is functionally capable of protecting cells from subsequent infection with the arboviruses Vesicular Stomatitis virus and Kunjin virus. These results represent a novel example of an invertebrate DNA virus activating a canonically RNA sensing pathway in the mammalian innate immune response, which reduces viral load of ensuing arboviral infection.
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页数:21
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