INSERM U932, Immunity and Cancer Unit, Institut Curie, Paris, France.
Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM U1104, CNRS UMR7280, 13288 Marseille, France.
Science. 2015 Sep 11;349(6253):1232-6. doi: 10.1126/science.aab3628. Epub 2015 Jul 30.
Infected cells detect viruses through a variety of receptors that initiate cell-intrinsic innate defense responses. Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) is a cytosolic sensor for many DNA viruses and HIV-1. In response to cytosolic viral DNA, cGAS synthesizes the second messenger 2'3'-cyclic GMP-AMP (cGAMP), which activates antiviral signaling pathways. We show that in cells producing virus, cGAS-synthesized cGAMP can be packaged in viral particles and extracellular vesicles. Viral particles efficiently delivered cGAMP to target cells. cGAMP transfer by viral particles to dendritic cells activated innate immunity and antiviral defenses. Finally, we show that cell-free murine cytomegalovirus and Modified Vaccinia Ankara virus contained cGAMP. Thus, transfer of cGAMP by viruses may represent a defense mechanism to propagate immune responses to uninfected target cells.
受感染的细胞通过各种受体来检测病毒，这些受体启动细胞内在的先天防御反应。环鸟苷酸-腺苷酸合酶（cGAS）是许多 DNA 病毒和 HIV-1 的细胞质传感器。cGAS 对细胞质中的病毒 DNA 作出反应，合成第二信使 2'3'-环鸟苷酸-腺苷酸（cGAMP），从而激活抗病毒信号通路。我们发现，在产生病毒的细胞中，cGAS 合成的 cGAMP 可以被包装在病毒颗粒和细胞外囊泡中。病毒颗粒有效地将 cGAMP 递送到靶细胞。病毒颗粒传递 cGAMP 给树突状细胞，激活先天免疫和抗病毒防御。最后，我们发现无细胞的鼠巨细胞病毒和改良型安卡拉牛痘病毒含有 cGAMP。因此，病毒传递 cGAMP 可能代表了一种防御机制，以将免疫反应传播到未感染的靶细胞。
