HIV-1 transforms the monocyte plasma membrane proteome.
How HIV-1 affects the monocyte proteome is incompletely understood. We posit that one functional consequence of virus-exposure to the monocyte is the facilitation of protein transformation from the cytosol to the plasma membrane (PM). To test this, cell surface labeling with CyDye fluorophores followed by 2 dimensional differential in-gel electrophoresis (2D DIGE) and liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed. Fifty three percent of HIV-1 induced proteins were PM associated. These were linked, in large measure, to cellular activation and oxidative stress. They included, but not limited to, biliverdin reductase, leukotriene hydrolase A(4), heat shock protein 70, and cystatin B. HIV-1 induced PM protein translocation was associated with cathepsin B- and caspase 9, 3-dependent apoptosis. In contrast, PMA-treated monocytes bypassed caspase 3, 9 pathways and lead to cathepsin B-dependent necrosis. These results demonstrate that HIV-1 uniquely affects monocyte activation and oxidative stress. These do not affect viral infection dynamics but are linked to stress-induced cell death.
Department of Pharmacology and Experimental Neuroscience, Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Irena
I
Kadiu
Tong
T
Wang
Joshua D
JD
Schlautman
Larisa
L
Dubrovsky
Pawel
P
Ciborowski
Michael
M
Bukrinsky
Howard E
HE
Gendelman
D002273:Carcinogens / Q000494:pharmacology; D002401:Cathepsin B / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004851:Epoxide Hydrolases / Q000187:drug effects / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D020543:Proteome / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology; D014815:Vitamins / Q000494:pharmacology
D002273:Carcinogens; D018840:HSP70 Heat-Shock Proteins; D020543:Proteome; D014815:Vitamins; D014810:Vitamin E; D004851:Epoxide Hydrolases; D002401:Cathepsin B; D013755:Tetradecanoylphorbol Acetate; C043134:leukotriene A4 hydrolase