The Function Of HLA-G In HTLV-1 Virus Infection Immunity

BackgroundHuman T-cell leukemia virus type 1(HTLV-1)is aδretrovirus,which can be transmitted by clinical transfusion,drug injection or sexual contact.After virus infection,HTLV-1 can infect a variety of innate immune cells and cause damage to their functions,resulting in their successful escape from immune surveillance for up to 20 years.As an endogenous antigen,HTLV-1 is mainly presented to T lymphocytes by histocompatibility complex class I molecule(MHCⅠ)to recognize and induce immune response.Therefore,MHC-I molecule plays an important role in the process of HTLV-1 infection.Human leukocyte antigen-G(HLA-G)is a functional non-classical MHC-class I molecule.It can inhibit the proliferation of CD4~+T cells and antigen presentation of dendritic cells,inhibit the kill functions of NK cells and CD8~+cells,and promote the expression of inhibitory receptors by binding with specific receptors expressed by immune cells.HLA-G has the function of immune tolerance and plays a role in inducing HIV to escape from the immune system,so will HIV-like retrovirus HTLV-1 also induce high expression of HLA-G in infected cells?Does overexpression of HLA-G affect HTLV-1 replication or evasion of the immune system?It remains to be further studied.ObjectiveTo study the expression of human leukocyte antigen G(HLA-G)in human T lymphoblastic leukemia virus type 1(HTLV-1)infection,and to explore the function and mechanism of HLA-G in HTLV-1 host immune response.Methods1.MT2 cells(HTLV-1~+T cells)were co-cultured with HeLa and THP1 cells respectively for 24 hours.The model of HTLV-1 virus infection was established by cell co-culture system of MT2-HeLa and MT2-THP1.qRT-PCR was used to detect the expression of HLA-G isoform mRNA in host cells after virus infection.2.Jurkat cells(HTLV-1~-T cells)were co-cultured with HeLa and THP1 cells respectively for 24 hours as negative control group;MT2 cells was co-cultured with HeLa and THP1 cells respectively for 24 hours as the experimental group.The expression of HLA-G protein in host cells after infection was detected by Western blot.3.We stained HeLa and THP1 cells with FITC fluorescence by using specific antibodies that can recognize membrane-bound HLA-G1.Detection of HLA-G1expression in host cells after infection by flow cytometry.4.We upregulated the expression of HLA-G in HeLa cells by transfection,and then infected the cells with HTLV-1 to verify the expression of its characteristic virus protein Tax at the protein level.5.We used siRNA technology to silence the HLA-G gene in HeLa cells,and then infected the cells with HTLV-1 to verify the expression of its characteristic virus protein Tax at the protein level.Results1.HeLa and THP1 cells infected by HTLV-1 could be induced to express HLA-G isoforms mRNA differently,mainly HLA-G1 and G5,while other isomers had no significant change.2.The results of Western blot showed that the expression of HLA-G protein was significantly up-regulated in HeLa cells after being infected by HTLV-1,and the expression of HLA-G protein was induced in THP1 cells.3.The results of flow cytometry showed that the expression of HLA-G1 was significantly up-regulated by HTLV-1 virus in HeLa cells,and the expression of HLA-G1was significantly increased in THP1 cells.Compared with the control group,the difference was statistically significant(P<0.05).4.The viral protein Tax of HeLa cells overexpressing HLA-G was significantly increased after being infected by HTLV-1 virus.The results showed that with the high expression of HLA-G,the expression of protein increased significantly.5.The protein in HeLa cells silenced by HLA-G gene was significantly decreased after being infected by HTLV-1 virus.It showed that with the low expression of HLA-G,the expression of protein decreased significantly.ConclusionThe expression of HLA-G,immune tolerance molecule,increases significantly after being infected by HTLV-1,and the high expression of HLA-G contributes to the transmission and replication of HTLV-1 virus,which may be one of the reasons for persistent infection of HTLV-1 virus.