Transmission of innate immune signaling by packaging of cGAMP in viral particles
Transmission of innate immune signaling by packaging of cGAMP in viral particles
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DOI：
10.1126/science.aab3628
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发表时间：
2015-09-11
期刊：
影响因子：
56.9
通讯作者：
Manel, Nicolas
中科院分区：
文献类型：
--
作者：
Gentili, Matteo;Kowal, Joanna;Manel, Nicolas
受感染的细胞通过各种受体检测病毒，这些受体启动细胞固有的天然防御反应。环磷酸鸟苷(GMP)-一磷酸腺苷(AMP)合成酶(CGAS)是许多DNA病毒和HIV-1的胞浆感受器。CGAS响应胞浆病毒DNA，合成第二信使2‘3’-环状GMP-AMP(CGAMP)，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可以包装在病毒颗粒和细胞外小泡中。病毒颗粒有效地将cGAMP运送到靶细胞。CGAMP通过病毒颗粒转移到树突状细胞，激活先天免疫和抗病毒防御。最后，我们发现无细胞小鼠巨细胞病毒和改良的痘苗病毒安卡拉病毒含有cGAMP。因此，病毒转移cGAMP可能代表了一种将免疫反应传播到未感染的靶细胞的防御机制。
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.