一篇是由法国国家健康与医学研究院 Nicolas Manel教授实验室发表。研究人员发现用表达cGAS的慢病毒去感染单核细胞（monocyte），结果发现，与对照慢病毒相比， 表达cGAS的慢病毒能够激活单核细胞分化成树突状细胞（DCs）。而且，在外转质粒表达cGAS的细胞中组装的HIV-1的病毒样颗粒（VLPs）也能够激活DCs。有意思的是，生化分析发现这些VLPs中不含cGAS蛋白，但是还有cGAMP小分子。除了在HIV-1，研究人员还发现疱疹病毒mCMV和痘病毒MVA的病毒粒子里也有cGAMP的存在。病毒粒子中cGAMP有什么作用呢？研究人员发现用包含cGAMP的VLPs感染细胞后能够抵抗随后的HSV-1感染，说明这是一种激活宿主抗病毒免疫反应新机制。
作者: ipsvirus 时间: 2015-8-4 20:54 Transmission of innate immune signaling by packaging of cGAMP in viral particles
Matteo Gentili1,2, Joanna Kowal1,2,*, Mercedes Tkach1,2,*, Takeshi Satoh1,2, Xavier Lahaye1,2, Cécile Conrad1,2, Marilyn Boyron3, Bérangère Lombard4, Sylvère Durand5, Guido Kroemer5, Damarys Loew4, Marc Dalod3, Clotilde Théry1,2,6, Nicolas Manel1,2,6,7,†
Infected cells detect viruses through a variety of receptors that initiate cell-intrinsic innate defense responses. Cyclic GMP-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 the attenuated human poxvirus vaccine Modified Vaccinia Ankara contained cGAMP. Thus transfer of cGAMP by viruses may represent a defense mechanism to propagate immune responses to uninfected target cells.
A. Bridgeman1, J. Maelfait1, T. Davenne1, T. Partridge2, Y. Peng1, A. Mayer1, T. Dong1, V. Kaever3, P. Borrow2, J. Rehwinkel1,*
Cyclic GMP-AMP synthase (cGAS) detects cytosolic DNA during virus infection and induces an antiviral state. cGAS signals by synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING). We show that cGAMP is incorporated into viral particles, including lentivirus and herpesvirus virions, when these are produced in cGAS-expressing cells. Virions transferred cGAMP to newly infected cells and triggered a STING-dependent antiviral program. These effects were independent of exosomes and viral nucleic acids. Our results reveal a way by which a signal for innate immunity is transferred between cells, potentially accelerating and broadening antiviral responses. Moreover, infection of dendritic cells with cGAMP-loaded lentiviruses enhanced their activation. Loading viral vectors with cGAMP therefore holds promise for vaccine development.
