Glutamylation of an HIV-1 protein inhibits the immune response by hijacking STING

Qian, Gui1,2; Zhang, Yihua1,2; Liu, Yinan1,2; Li, Manman1,2; Xin, Bowen1,2; Jiang, Wenyi1,2; Han, Wendong3; Wang, Yu4; Tang, Xian5; Li, Liuyan1,2; Zhu, Lingyan1,2; Sun, Tao1,2; Yan, Bo1,2; Zheng, Yongtang6; Xu, Jianqing7,8; Ge, Baoxue9; Zhang, Zheng5; Yan, Dapeng1,2

2023-05-30

10.1016/j.celrep.2023.112442

CELL REPORTS   影响因子和分区

2211-1247

Cyclic GMP-AMP synthase (cGAS) recognizes Y-form cDNA of human immunodeficiency virus type 1 (HIV-1) and initiates antiviral immune response through cGAS-stimulator of interferon genes (STING)-TBK1-IRF3-type I interferon (IFN-I) signalingcascade. Here, we report that the HIV-1 p6 protein suppresses HIV-1-stimulated expression of IFN-I and promotes immune evasion. Mechanistically, the glutamylated p6 at residue Glu6 in-hibits the interaction between STING and tripartite motif protein 32 (TRIM32) or autocrine motility factor recep-tor (AMFR). This subsequently suppresses the K27-and K63-linked polyubiquitination of STING at K337, there-fore inhibiting STING activation, whereas mutation of the Glu6 residue partially reverses the inhibitory effect. However, CoCl2, an agonist of cytosolic carboxypeptidases (CCPs), counteracts the glutamylation of p6 at the Glu6 residue and inhibits HIV-1 immune evasion. These findings reveal a mechanism through which an HIV-1 protein mediates immune evasion and provides a therapeutic drug candidate to treat HIV-1 infection.

SCI

英语

其他

National Natural Science Foundation of China["32270973","31972900"] ; Shanghai Pilot Program for Basic Research[21TQ017] ; Program of Shanghai Academic Research Leader[21XD1402900] ; Natural Science Foundation of Shanghai[21ZR1481400] ; National KeyResearch and Development Program of China[2022YFC2304704]

Cell Biology

Cell Biology

WOS:000989198800001

CELL PRESS

Web of Science

1.Fudan Univ, Shanghai Inst Infect Dis & Biosecur, Sch Basic Med Sci, Dept Immunol, Shanghai 200032, Peoples R China
2.Fudan Univ, Shanghai Publ Hlth Clin Ctr, Shanghai 200032, Peoples R China
3.Fudan Univ, Biosafety Level Lab 3, Shanghai 200032, Peoples R China
4.Army Med Univ, Coll Pharm, Natl Engn Res Ctr Immunol Prod, Dept Microbiol, Chongqing 400038, Peoples R China
5.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Inst Hepatol, Natl Clin Res Ctr Infect Dis,Sch Med, Shenzhen 518112, Guangdong, Peoples R China
6.Chinese Acad Sci, Kunming Inst Zool, KIZ CUHK Joint Lab Bioresources & Mol Res Common D, Key Lab Anim Models & Human Dis Mech, Kunming 650223, Yunnan, Peoples R China
7.Fudan Univ, Zhongshan Hosp, Shanghai Key Lab Organ Transplantat, Shanghai 200032, Peoples R China
8.Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China
9.Tongji Univ, Sch Med, Shanghai Pulm Hosp, Shanghai TB Key Lab, Shanghai 200433, Peoples R China

Qian, Gui,Zhang, Yihua,Liu, Yinan,et al. Glutamylation of an HIV-1 protein inhibits the immune response by hijacking STING[J]. CELL REPORTS,2023,42(5).

Qian, Gui.,Zhang, Yihua.,Liu, Yinan.,Li, Manman.,Xin, Bowen.,...&Yan, Dapeng.(2023).Glutamylation of an HIV-1 protein inhibits the immune response by hijacking STING.CELL REPORTS,42(5).

Qian, Gui,et al."Glutamylation of an HIV-1 protein inhibits the immune response by hijacking STING".CELL REPORTS 42.5(2023).