title: FOXO3, IRF4, and xIAP Are Correlated with Immune Activation in HIV-1-Infected Men Who Have Sex with Men During Early HIV Infection.
abstract: Forkhead box O (FOXO)1, FOXO3, interferon regulatory factor (IRF)4, X-linked inhibitor of apoptosis protein (xIAP), and E74-like factor (ELF)4 have been described as important regulators of T cell functions and differentiation. However, whether these molecules are associated with HIV-1 disease progression is still unknown. In this study, we showed that the levels of FOXO3, IRF4, and xIAP mRNA in rapid progressors (RPs) were significantly higher than in HIV-negative healthy controls (HCs). Moreover, FOXO3 expression was positively correlated with HIV-1 viral load and CD4+T cell activation. Remarkably, increased CD4+and CD8+T cell activation was apparent in RPs compared with typical progressors and HCs. In addition, a profile of higher apoptosis, more CD8+TEMcells, and fewer CD4+and CD8+Naive T cells were observed in early HIV infection patients with low CD4+T cell counts. Furthermore, in vitro, IRF4 and xIAP expression was enhanced in peripheral blood mononuclear cells from healthy people following T cell receptor stimulation. T cell activation was decreased by treatment with siRNA inhibiting FOXO3, IRF4, and xIAP. Our results show that significantly increased levels of FOXO3, IRF4, and xIAP mRNA in Chinese HIV-1-infected patients were related to T cell immune activation, implicating them as potential targets for developing new therapeutic avenues to slow down HIV-1 disease progression.
authors.affiliation: 1 Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University , Shenyang, China .|2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases , Hangzhou, China .
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 1 Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University , Shenyang, China .|2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases , Hangzhou, China .
authors.forename: Zining
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: 1 Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University , Shenyang, China .|2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases , Hangzhou, China .
authors.forename: Sijia
authors.initials: S
authors.lastname: He
authors.affiliation: 1 Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University , Shenyang, China .|2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases , Hangzhou, China .
authors.forename: Yajing
authors.initials: Y
authors.lastname: Fu
authors.affiliation: 1 Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University , Shenyang, China .|2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases , Hangzhou, China .
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 1 Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University , Shenyang, China .|2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases , Hangzhou, China .
authors.forename: Nan
authors.initials: N
authors.lastname: Yi
authors.affiliation: 1 Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University , Shenyang, China .|2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases , Hangzhou, China .
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: 1 Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University , Shenyang, China .|2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases , Hangzhou, China .
authors.forename: Wenqing
authors.initials: W
authors.lastname: Geng
authors.affiliation: 1 Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University , Shenyang, China .|2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases , Hangzhou, China .
authors.forename: Hong
authors.initials: H
authors.lastname: Shang
mesh_terms: D000328:Adult; D002681:China; D000071316:Forkhead Box Protein O3 / Q000032:analysis*; D015658:HIV Infections / Q000473:pathology*; D015497:HIV-1 / Q000302:isolation & purification; D018451:Homosexuality, Male; D006801:Humans; D050835:Interferon Regulatory Factors / Q000032:analysis*; D008213:Lymphocyte Activation; D008297:Male; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000032:analysis*; D000099218:Interferon Regulatory Factor-4
chemical_list: D000071316:Forkhead Box Protein O3; D050835:Interferon Regulatory Factors; D051636:X-Linked Inhibitor of Apoptosis Protein; D000099218:Interferon Regulatory Factor-4; C499517:FOXO3 protein, human; C496866:XIAP protein, human
keywords: HIV; HIV in men who have sex with men (MSM); T cell immunity; immune activation; molecular biology