SerpinE1 regulating HIV-1 replication in macrophages through the JAK/STAT pathway
Objective:To explore the relationship between serine protease inhibitor E family member 1(Ser-pinE1)and human immunodeficiency virus type 1(HIV-1)infection,as well as the role and mechanism of Ser-pinE1 as a protease inhibitor in macrophages in the process of HIV infection.Methods:Groups were matched ac-cording to age and gender characteristics to recruit untreated HIV infected patients[HIV ART(-)group]and healthy controls(HC group),and the expression of SerpinE1 mRNA in peripheral blood mononuclear cells(PBMCs)was detected.SerpinE1 knockdown cells were constructed on THP-1 cells(knock-down SerpinE1 group),infected or uninfected with HIV BaL.The expression levels of HIV-p24 and interferon(IFN)-α protein were detected by enzyme-linked immunosorbent assay(ELISA).The differential genes and KEGG enrichment pathways between knock-down SerpinE1 group and control group after exposure were analyzed by transcriptome sequencing.The mRNA expression levels of HIV Gag,Toll-like receptor 7(TLR7),Toll-like receptor 8(TLR8),interleukin-1β(IL-1β),MX dynamin-like GTPase 1(MX1)and MX2 were detected by reverse transcription-quan-titative PCR(RT-qPCR).The protein expression levels of JAK2,STAT1,STAT2,SATA4,IL-1β and MX1 were detected by western blotting.Results:Compared with the HC group,SerpinE1 was lowly expressed in in the HIV ART(-)group,and could be down-regulated by HIV in THP-1-derived macrophages(P＜0.05).Knockdown of SerpinE1 expression down-regulated HIV-p24 protein expression and HIV Gag mRAN expression,promoted IFN-α protein secretion level,and enhanced the expression of TLR7,TLR8,Janus kinase 2(JAK2),signal trans-ducer and activator of transcription(STAT)protein family members STAT1,STAT2,STAT4,IL-1β,MX1,and MX2(P＜0.05).Conclusion:SerpinE1 may reduce the release of IFN by inhibiting the activation of TLR7 and TLR8 signaling pathways,and then inhibit the JAK/STAT pathway and its induced expression of various IFN stimulated genes and IFN-related factors,thereby promoting HIV-1 infection and replication.
serine protease inhibitor E family member 1macrophagesinterferon-alphaJAK/STATanti-hu-man immunodeficiency virus type 1
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