Proteomic analysis of the cellular responses induced in uninfected immune cells by cell-expressed X4 HIV-1 envelope.
HIV-1 envelope gp120 and gp41 glycoproteins (Env), expressed at the cell surface, induce uninfected CD4 T-cell death, but the molecular mechanisms leading to this demise are still largely unknown. To better understand these events, we analyzed by a proteomic approach the differential protein expression profile of two types of uninfected immune cells after their coculture for 1-3 days with cells that express, or not, Env. First, umbilical cord blood mononuclear cells (UCBMCs) were used to approach the in vivo situation, i.e., blood uninfected naive cells that encounter infected cells. Second, we used the A2.01/CD4.403 T-cell line expressing wild type CXCR4 and a truncated form of CD4 that still undergoes Env-mediated apoptosis, independently of CD4 signaling. After coculture with cells expressing Env, 35 and 39 proteins presenting an altered expression in UCBMCs and the A2.01/CD4.403 T-cell line, respectively, were identified by mass-spectrometry. Whatever the cell type analyzed, the majority of these proteins are involved in degradation processes, redox homeostasis, metabolism and cytoskeleton dynamics, and linked to mitochondrial functions. This study provides new insights into the events that sequentially occur in bystander T lymphocytes after contact with HIV-infected cells and leading, finally, to apoptotic cell death.
Molina
Laurence
L
Centre National de la Recherche Scientifique (CNRS) FRE3009, Complex System Modelling and Engineering for Diagnostic, Faculté de Pharmacie, Montpellier, France.
Grimaldi
Marina
M
Robert-Hebmann
Véronique
V
Espert
Lucile
L
Varbanov
Mihayl
M
Devaux
Christian
C
Granier
Claude
C
Biard-Piechaczyk
Martine
M
D001343:Autophagy / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology / Q000648:ultrastructure; D016923:Cell Death / Q000276:immunology; D002460:Cell Line; D018920:Coculture Techniques; D015180:Electrophoresis, Gel, Two-Dimensional; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology; D013058:Mass Spectrometry; D009000:Monocytes / Q000276:immunology / Q000648:ultrastructure; D010449:Peptide Mapping; D020543:Proteome / Q000032:analysis; D040901:Proteomics / Q000379:methods*; D017382:Reactive Oxygen Species / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012235:Rhodamines; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors
D005456:Fluorescent Dyes; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D018840:HSP70 Heat-Shock Proteins; D020543:Proteome; D017382:Reactive Oxygen Species; D019718:Receptors, CXCR4; D012235:Rhodamines