Oncotarget

Research Papers:

HIV-1 Gp120 clade B/C induces a GRP78 driven cytoprotective mechanism in astrocytoma

Sheila N. López, Madeline Rodríguez-Valentín, Mariela Rivera, Maridaliz Rodríguez, Mohan Babu, Luis A. Cubano, Huangui Xiong, Guangdi Wang, Lilia Kucheryavykh and Nawal M. Boukli _

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Oncotarget. 2017; 8:68415-68438. https://doi.org/10.18632/oncotarget.19474

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Abstract

Sheila N. López1, Madeline Rodríguez-Valentín1, Mariela Rivera1, Maridaliz Rodríguez1, Mohan Babu2, Luis A. Cubano1, Huangui Xiong3, Guangdi Wang4, Lilia Kucheryavykh5 and Nawal M. Boukli1

1Biomedical Proteomics Facility, Department of Microbiology and Immunology, Universidad Central del Caribe, School of Medicine, Bayamón, PR, USA

2Department of Biochemistry, Research and Innovation Center, University of Regina, Saskatchewan, Canada

3Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

4RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA, USA

5Department of Biochemistry, Universidad Central del Caribe, School of Medicine, Bayamón, PR, USA

Correspondence to:

Nawal M. Boukli, email: nawal.boukli@uccaribe.edu

Keywords: HIV-1 clades B and C, Gp120, GRP78, quantitative proteomics (tandem mass tag), unfolded protein response (UPR)

Received: March 24, 2017    Accepted: June 28, 2017    Published: July 22, 2017

ABSTRACT

HIV-1 clades are known to be one of the key factors implicated in modulating HIV-associated neurocognitive disorders. HIV-1 B and C clades account for the majority of HIV-1 infections, clade B being the most neuropathogenic. The mechanisms behind HIV-mediated neuropathogenesis remain the subject of active research. We hypothesized that HIV-1 gp120 clade B and C proteins may exert differential proliferation, cell survival and NeuroAIDS effects in human astrocytoma cells via the Unfolded Protein Response, an endoplasmic reticulum- based cytoprotective mechanism. The differential effect of gp120 clade B and C was evaluated using for the first time a Tandem Mass Tag isobaric labeling quantitative proteomic approach. Flow cytometry analyses were performed for cell cycle and cell death identification. Among the proteins differentiated by HIV-1 gp120 proteins figure cytoskeleton, oxidative stress, UPR markers and numerous glycolytic metabolism enzymes. Our results demonstrate that HIV-1 gp120 B induced migration, proliferative and protective responses granted by the expression of GRP78, while HIV-1 gp120 C induced the expression of key inflammatory and pro-apoptotic markers. These novel findings put forward the first evidence that GRP78 is a key player in HIV-1 clade B and C neuropathogenic discrepancies and can be used as a novel target for immunotherapies.


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