Viruses transfer the antiviral second messenger cGAMP between cells

被引：219

作者：

Bridgeman, A. ^{[1
]}

Maelfait, J. ^{[1
]}

Davenne, T. ^{[1
]}

Partridge, T. ^{[2
]}

Peng, Y. ^{[1
]}

Mayer, A. ^{[1
]}

Dong, T. ^{[1
]}

Kaever, V. ^{[3
]}

Borrow, P. ^{[2
]}

Rehwinkel, J. ^{[1
]}

机构：

[1] Univ Oxford, Radcliffe Dept Med, Weatherall Inst Mol Med, MRC,Human Immunol Unit, Oxford OX3 9DS, England

[2] Univ Oxford, Nuffield Dept Med, Oxford OX3 7FZ, England

[3] Hannover Med Sch, Inst Pharmacol, Res Core Unit Metabol, D-30625 Hannover, Germany

来源：

SCIENCE | 2015年 / 349卷 / 6253期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

CYCLIC GMP-AMP; INNATE IMMUNE SENSOR; DNA; HIV-1; RECOGNITION; SYNTHASE; REVEALS; ROLES;

D O I：

10.1126/science.aab3632

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：1228 / 1232

页数：7

共 27 条

[1]

Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP [J].