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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.

Author information

1
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
2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases , Hangzhou, China .

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+ 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.

KEYWORDS:

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

PMID:
27841661
DOI:
10.1089/AID.2015.0316
[Indexed for MEDLINE]

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