Abstract
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.
Highlights
The innate immune response is composed of a set of defense mechanisms that protect the host from microbial pathogens
We examined secreted IFN-β from the cell culture supernatant as an indication an innate immune response, and observed that IFN-β is secreted in response to Iridescent Virus 6 (IIV-6), but not Drosophila C virus (DCV) in infected mouse embryonic fibroblasts (MEFs) (Fig 1B)
Based on the result that Retinoic acid-inducible gene I (RIG-I) significantly contributes to an innate immune response in IIV-6-infected MEFs, we asked if IIV-6 would replicate in RIG-I-/- MEFs; like in wild-type MEFs, we observed no significant increase in IIV-6 replication in RIG-I deficient MEFs (S5 Fig)
Summary
The innate immune response is composed of a set of defense mechanisms that protect the host from microbial pathogens. This initial sensing of pathogens occurs through the activation of host pattern recognition receptors (PRRs) by pathogen-associated molecular patterns (PAMPs), which are conserved molecular motifs unique to microbes or are generated during the pathogen’s cycle of infection [1]. Significant progress has been made during the past two decades in understanding how innate immune signaling pathways are activated and, in turn, shape adaptive immunity. Much of this research has focused on the immune response to viruses that are transmitted by an insect vector, such as West Nile virus (WNV) and Dengue. IIV-6 Activates Immune Response in Mammalian Cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
