Invertebrate Iridescent Virus 6, a DNA Virus, Stimulates a Mammalian Innate Immune Response through RIG-I-Like Receptors.
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 interferon-dependent 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 (RLR) pathway, and not the canonical DNA sensing pathway via cGAS/STING. We further show that RNA polymerase III is required for maximal IFN-β 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.
School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of America.|NIH Protein Biotechnology Graduate Training Program, Washington State University, Pullman, Washington, United States of America.
Laura R H
LR
Ahlers
School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of America.
Reginaldo G
RG
Bastos
School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of America.
Aoi
A
Hiroyasu
School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of America.
Alan G
http://orcid.org/0000-0001-6394-332X
AG
Goodman
D000818:Animals; D002460:Cell Line; D000071457:DEAD Box Protein 58 / Q000502:physiology*; D004266:DNA Virus Infections / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D015151:Immunoblotting; D016899:Interferon-beta / Q000378:metabolism; D007497:Iridoviridae / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D034622:RNA Interference; D012320:RNA Polymerase III / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016899:Interferon-beta; D012320:RNA Polymerase III; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58