Affiliation:
1. Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University 1 State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science , , Tianjin 300071 , China
2. the First Affiliated Hospital of Henan University, Henan University 2 Joint National Laboratory for Antibody Drug Engineering , , Kaifeng 475000 , China
Abstract
ABSTRACT
Stimulator of IFN genes (STING; also known as STING1) is an important adaptor protein for detecting cytosolic double-stranded DNA, which can come from HIV infection. Several HIV proteins, such as p6, Vpx and Vif, can influence STING-mediated innate immunity, but the function of p17 is still unknown. In this study, we find that HIV-1 p17, but not HIV-2 p17 or SIV p17, promotes STING signaling induced by cyclic GMP-AMP (cGAMP) treatment. Mechanistically, HIV-1 p17 binds to Obg-like ATPase 1 (OLA1) and inhibits the regulation of STING by OLA1. Here, OLA1 interacts with STING and inhibits the translocation and phosphorylation of STING upon cGAMP stimulation. Furthermore, compared with HIV-2 and SIV, the ATPase and GTPase activities of OLA1 are only promoted by HIV-1 p17. Our study shows that the p17 of HIV-1, but not HIV-2 or SIV, promotes STING-mediated innate immunity by interfering the interaction between OLA1 and STING, thus providing a new clue for specific immune activation of HIV-1.
Funder
National Natural Science Foundation of China
Tianjin Natural Science Foundation
China Postdoctoral Science Foundation
Science and Technology Department of Henan Province
Publisher
The Company of Biologists