%0 Journal Article
%1 Xu2016443
%A Xu, S
%A Ducroux, A
%A Ponnurangam, A
%A Vieyres, G
%A Franz, S
%A Müsken, M
%A Zillinger, T
%A Malassa, A
%A Ewald, E
%A Hornung, V
%A Barchet, W
%A Häussler, S
%A Pietschmann, T
%A Goffinet, C
%D 2016
%E Microbe, Cell Host
%J Cell Host & Microbe
%K pietschmann
%N 4
%P 443-457
%T cGAS-Mediated Innate Immunity Spreads Intercellularly through HIV-1 Env-Induced Membrane Fusion Sites
%V 20
%X Summary Upon sensing cytoplasmic retroviral \DNA\ in infected cells, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide cGAMP, which activates \STING\ to trigger a type I interferon (IFN) response. We find that membrane fusion-inducing contact between donor cells expressing the \HIV\ envelope (Env) and primary macrophages endogenously expressing the \HIV\ receptor \CD4\ and coreceptor enable intercellular transfer of cGAMP. This cGAMP exchange results in STING-dependent antiviral \IFN\ responses in target macrophages and protection from \HIV\ infection. Furthermore, under conditions allowing cell-to-cell transmission of HIV-1, infected primary T cells, but not cell-free virions, deliver cGAMP to autologous macrophages through HIV-1 Env and CD4/coreceptor-mediated membrane fusion sites and induce a STING-dependent, but cGAS-independent, \IFN\ response in target cells. Collectively, these findings identify an infection-specific mode of horizontal transfer of cGAMP between primary immune cells that may boost antiviral responses, particularly in infected tissues in which cell-to-cell transmission of virions exceeds cell-free infection.