Cyclic GMP-AMP synthase ( cGAS) inhibits the replication of human T cell leukemia virus type 1 (HTLV-1) in HeLa cells through regulating innate immune response
10.3760/cma.j.issn.0254-5101.2017.11.004
- VernacularTitle:cGAS通过调控固有免疫应答抑制HTLV-1在HeLa细胞中复制
- Author:
Lingling MA
1
,
2
;
453003 新乡医学院医学检验学院科研创新班
;
Zhixiang GUO
;
Di SONG
;
Yue LIU
;
Yuhan CUI
;
Yuhe GUAN
;
Bo YANG
;
Jie WANG
Author Information
1. 453003 新乡医学院河南省免疫与靶向药物重点实验室
2. 453003 新乡医学院医学检验学院科研创新班
- Keywords:
Cyclic GMP-AMP synthase ( cGAS);
Human T cell leukemia virus type 1 ( HTLV-1);
DNA sensor;
Retrovirus
- From:
Chinese Journal of Microbiology and Immunology
2017;37(11):822-826
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the function and the possible mechanism of cyclic GMP-AMP synthase (cGAS), a DNA sensor, in HeLa cells during human T cell leukemia virus type 1 (HTLV-1) in-fection.Methods HeLa cells were co-cultured with MT2 cells (HTLV-1-positive T cells) and then detec-ted by immunoblot assay to analyze the changes in the expression of cGAS .A hemagglutinin ( HA)-tagged cGAS plasmid was constructed and transfected into HeLa cells .Twenty-four hours after transfection , these cells were co-cultured with MT2 cells for another 24 hours.Immunoblot assay was used to detect the expres-sion of HTLV-1 proteins Tax and p19.Real-time PCR was performed to measure the expression of HTLV-1 Tax, p19, Env, HBZ and px at mRNA level .Immunoblot assay was also used to analyze the phosphorylation of interferon regulatory factor 3 (IRF3) and p65.Expression of interferon (IFN)-β, IFN-gamma-inducible protein 10 ( IP-10 ) , RANTES ( regulated on activation , normal T cell expressed and secreted ) and tumor necrosis factor (TNF)-αwas detected by real-time PCR assay.Results Expression of cGAS was enhanced in HeLa cells after co-cultured with MT2 cells.Compared with control cells , the HeLa cells that were trans-fected with cGAS plasmid showed lower levels of Tax and p 19 proteins, suppressed expression of HTLV-1 Tax, p19, Env, HBZ and px at mRNA level , enhanced phosphorylation of IRF 3 and p65, and higher levels of IFN-β, IP-10, RANTES and TNF-αafter co-cultured with MT2 cells.Conclusion cGAS might promote the innate immune response and inhibit HTLV-1 replication in HTLV-1-infected HeLa cells .
