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
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) infection. 
 
 
Methods 
HeLa cells were co-cultured with MT2 cells (HTLV-1-positive T cells) and then detected 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 expression 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)-α was 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 transfected with cGAS plasmid showed lower levels of Tax and p19 proteins, suppressed expression of HTLV-1 Tax, p19, Env, HBZ and px at mRNA level, enhanced phosphorylation of IRF3 and p65, and higher levels of IFN-β, IP-10, RANTES and TNF-α after co-cultured with MT2 cells. 
 
 
Conclusion 
cGAS might promote the innate immune response and inhibit HTLV-1 replication in HTLV-1-infected HeLa cells. 
 
 
Key words: 
Cyclic GMP-AMP synthase (cGAS); Human T cell leukemia virus type 1 (HTLV-1); DNA sensor; Retrovirus