HIV-1 Envelope Protein gp120 Promotes Proliferation and the Activation of Glycolysis in Glioma Cell.

Gabriel Valentín-Guillama,Nataliya Chorna,Nawal Boukli,Jose Pérez,Alfredo Quinones-Hinojosa,Vladimir Makarov,Jescelica Ortiz-Rivera,Lilia Kucheryavykh,Yuriy Kucheryavykh,Aníbal Valentín-Acevedo,Michael Inyushin,Sheila López

doi:10.3390/cancers10090301

Abstract

Patients infected with human immunodeficiency virus (HIV) are more prone to developing cancers, including glioblastomas (GBMs). The median survival for HIV positive GBM patients is significantly shorter than for those who are uninfected, despite the fact that they receive the same treatments. The nature of the GBM–HIV association remains poorly understood. In this study, we analyzed the effect of the HIV envelope glycoprotein gp120 on GBM cell proliferation. Specifically, we performed cell cycle, western blot, protein synthesis and metabolomics analysis as well as ATP production and oxygen consumption assays to evaluate proliferation and metabolic pathways in primary human glioma cell line, U87, A172 cells and in the HIVgp120tg/GL261 mouse model. Glioma cells treated with gp120 (100 ng/mL for 7–10 days) showed higher proliferation rates and upregulation in the expression of enolase 2, hexokinase and glyceraldehyde-3-phosphate dehydrogenase when compared to untreated cells. Furthermore, we detected an increase in the activity of pyruvate kinase and a higher glycolytic index in gp120 treated cells. Gp120 treated GBM cells also showed heightened lipid and protein synthesis. Overall, we demonstrate that in glioma cells, the HIV envelope glycoprotein promotes proliferation and activation of glycolysis resulting in increased protein and lipid synthesis.

Highlights

Patients infected with human immunodeficiency virus (HIV) are more predisposed to developing cancer, including glioblastoma (GBM) [1,2] and ten percent of patients with acquired immune deficiencyCancers 2018, 10, 301; doi:10.3390/cancers10090301 www.mdpi.com/journal/cancersCancers 2018, 10, 301 syndrome (AIDS) have brain tumors
The gp120 concentration we used has been reported in the literature as effective for inducing signaling in glioma cells and it is consistent with the gp120 serum concentration in HIV patients [32,33]
Taken our results demonstrate that the HIV-gp120 glycoprotein induces proliferation in glioma together, our results demonstrate that the HIV-gp120 glycoprotein induces proliferation in glioma cells

Summary

Introduction

Patients infected with human immunodeficiency virus (HIV) are more predisposed to developing cancer, including glioblastoma (GBM) [1,2] and ten percent of patients with acquired immune deficiency. Cancers 2018, 10, 301 syndrome (AIDS) have brain tumors. Multiple medical reports in HIV/AIDS patients indicate that GBM occurs at a higher frequency (5.4- to 45-fold increase) [4,5,6,7] and at a younger age [8] in individuals at various stages of HIV infection than in the general population. GBM tumors appear approximately 3 years after initial HIV infection [2]. CD4+ cell count at initial diagnosis of GBM is not correlated with survival suggesting that increased aggressive tumor behavior is not a direct outcome of immune deficiency [8]

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Conclusion