Research Projects (Third party funds)

Project

Characterisation of the cGAS-mediated DNA-sensing signaling in HIV infected T-cells

cytosolic DNA sensor cGAScytosolic DNA sensor cGAS

DFG Priority Programme 1923, "Innate Sensing and Restriction of Retroviruses"

Upon HIV-1 infection of T-cells, viral DNA can be sensed by the cytosolic DNA sensor cGAS. In cocultures with macrophages, HIV-1 Env-mediated membrane fusion pores allow the horizontal transfer of the cGAS product and cyclic dinucleotide cGAMP to macrophages, where it activates STING-dependent expression of antiviral cytokines and effector molecules (Xu und Ducroux et al., Cell Host & Microbe 2016). In monocultures of T-cells and macrophages, HIV-1 prevents or counteracts activation of this cellular defense mechanism. In contrast to the situation in macrophages, our understanding of the reasons for the lack of a detectable type I IFN response in HIV-1-infected T-cells is limited. In this project, we address the effectiveness of the cGAS-mediated DNA sensing pathway in primary T-cells and try to unravel potential explanations for the lack of IFN induction in this important HIV-1 target cell type.

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Funding agency

DFG - German Research Foundation

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