Invertebrate Iridescent Virus 6, a DNA Virus, Stimulates a Mammalian Innate Immune Response through RIG-I-Like Receptors.
Invertebrate Iridescent Virus 6, a DNA Virus, Stimulates a Mammalian Innate Immune Response through RIG-I-Like Receptors.
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DOI：
10.1371/journal.pone.0166088
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Goodman AG
中科院分区：
文献类型：
--
作者：
Ahlers LR;Bastos RG;Hiroyasu A;Goodman AG
昆虫不仅是哺乳动物病毒的主要媒介，而且也是昆虫限制性病毒的宿主，这些病毒可能会传播给哺乳动物。虽然哺乳动物对虫媒病毒的先天免疫反应已经被很好地研究了，但关于哺乳动物细胞如何对仅限于感染无脊椎动物的病毒做出反应的了解较少。在这里，我们证明了IIV-6，一种虹膜病毒科的DNA病毒，能够在哺乳动物细胞中诱导依赖于I型干扰素的抗病毒免疫反应。虽然IIV-6是一种DNA病毒，但我们证明了在IIV-6感染过程中激活的免疫反应是由RIG-I样受体(RLR)途径介导的，而不是通过cGAS/STIN的典型DNA传感途径。我们进一步表明，最大限度地分泌干扰素-β需要RNA聚合酶III，这表明病毒DNA是由这种酶转录成能够激活RLR途径的RNA物种。最后，我们证明了RLR驱动的哺乳动物对IIV-6的先天免疫反应在功能上能够保护细胞免受虫媒病毒水泡性口炎病毒和昆津病毒的感染。这些结果代表了一个新的例子，无脊椎动物DNA病毒激活了哺乳动物先天免疫反应中典型的RNA传感途径，从而减少了随后虫媒病毒感染的病毒负荷。
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.
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