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AIDS Res Hum Retroviruses. 2017 Feb;33(2):172-180. doi: 10.1089/AID.2015.0316. Epub 2016 Dec 22.

FOXO3, IRF4, and xIAP Are Correlated with Immune Activation in HIV-1-Infected Men Who Have Sex with Men During Early HIV Infection.

Zhang X1,2, Zhang Z1,2, He S1,2, Fu Y1,2, Chen Y1,2, Yi N1,2, Jiang Y1,2, Geng W1,2, Shang H1,2.

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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 .


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+ TEM cells, 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.


HIV; HIV in men who have sex with men (MSM); T cell immunity; immune activation; molecular biology

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