Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Synthetic Polypeptide Derived from Viral Macrophage Inflammatory Protein II Inhibit the Uninfected CD4+ T Cells Apoptosis Induced by HIV-1 Extracellular Nef

Gui-Jie An, Xiu-Ying Li, Han-Xiao Sun , Sha Liu, Jing-Guang Zhou, Qing Ding, Pi-Jin Wei, Guang Zhang

Institute of Genomic Medicine, College of Pharmacy, Jinan University, Guangzhou 510632, China;

For correspondence:- Han-Xiao Sun Email: sunhx718@163.com Tel:+8602038375022

Received: 19 December 2013 Accepted: 30 April 2014 Published: 23 May 2014

Citation: An G, Li X, Sun H, Liu S, Zhou J, Ding Q, et al. Synthetic Polypeptide Derived from Viral Macrophage Inflammatory Protein II Inhibit the Uninfected CD4+ T Cells Apoptosis Induced by HIV-1 Extracellular Nef. Trop J Pharm Res 2014; 13(5):683-688 doi: 10.4314/tjpr.v13i5.5

© 2014 The authors.
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Abstract

Purpose: To evaluate the potential role and cellular mechanism of the CXCR4 antagonist (N15P) derived from the N-terminal of viral macrophage inflammatory protein-II (vMIP-II) on the apoptosis induced by HIV-1 extracellular nef protein in vitro.

Method: Peripheral blood mononuclear cells (PBMCs) and Jurkat cells were treated with HIV-1 nef protein alone or together with N15P at different doses and time points. The competitive binding effect of N15P against nef was assessed via radioligand binding assays. Apoptosis was evaluated via terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay. The level of nuclear FOXO3a and phospho-FOXO3a was assessed by Western blotting.

Results: The interaction of ¹²⁵I-nef with Jurkat cells was inhibited by N15P in a dose-dependent manner, with IC₅₀ value of 0.3516 ng/ml. N15P protect against nef protein-induced apoptosis in a time- and concentration- dependent manner. The proapoptotic effect of extracellular nef protein in cells was associated with FOXO3a pathway and the changes in intracellular processes were blocked by N15P in a dose-dependent manner.

Conclusion: N15P inhibits the apoptosis of uninfected CD4⁺ T lymphocytes induced by HIV-1 extracellular nef protein. Therefore, N15P is a potential effective CXCR4 antagonist in the course of HIV and could prevent or delay the onset of AIDS.

Keywords: HIV-1, Nef, vMIP-II, Bystander lymphocytes, Apoptosis, FOXO3a, CXCR4 antagonist, Macrophage, Inflammation