title: Proteome and Protein Network Analyses of Memory T Cells Find Altered Translation and Cell Stress Signaling in Treated Human Immunodeficiency Virus Patients Exhibiting Poor CD4 Recovery.
abstract: Background.Human immunodeficiency virus (HIV) patients who experience poor CD4 T-cell recovery despite viral suppression during antiretroviral therapy (ART) are known as immunological nonresponders. The molecular mechanism(s) underlying incomplete immune restoration during ART is not fully understood.Methods.Label-free quantitative proteomics on single-cell type central memory T cells were used to reveal relative protein abundance changes between nonresponder, responder (good CD4 recovery during ART), and healthy individuals. Proteome changes were analyzed by protein pathway and network analyses and verified by selected reaction monitoring mass spectrometry.Results.Proteomic analysis across groups detected 155 significant proteins from 1500 nonredundant proteins. Pathway and network analyses revealed dysregulation in mammalian target of rapamycin and protein translation-related proteins and decreases in stress response-related proteins for nonresponder subjects compared with responders and controls. Actin cytoskeleton signaling was increased for HIV responders and nonresponders alike.Conclusions.Memory T cells from immunologic nonresponders have increases in proteins related to motility and protein translation and decreases in proteins capable of responding to cellular stresses compared with responders and controls. The potential for T cells to manage stress and modulate metabolism may contribute to their capacity to reconstitute a lymphopenic host.
authors.affiliation: Center for Proteomics and Bioinformatics; Pulmonary Critical Care and Sleep Medicine.
authors.forename: Sausan
authors.initials: S
authors.lastname: Azzam
authors.affiliation: Center for Proteomics and Bioinformatics.
authors.forename: Daniela
authors.initials: D
authors.lastname: Schlatzer
authors.affiliation: Center for Proteomics and Bioinformatics.
authors.forename: Sean
authors.initials: S
authors.lastname: Maxwell
authors.affiliation: Center for Proteomics and Bioinformatics.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.affiliation: Division of Infectious Diseases and HIV Medicine.
authors.forename: Douglas
authors.initials: D
authors.lastname: Bazdar
authors.affiliation: Department of Epidemiology and Biostatistics , Case Western Reserve University School of Medicine , Cleveland, Ohio.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Infectious Diseases and HIV Medicine.
authors.forename: Robert
authors.initials: R
authors.lastname: Asaad
authors.affiliation: Department of Epidemiology and Biostatistics , Case Western Reserve University School of Medicine , Cleveland, Ohio.
authors.forename: Jill
authors.initials: J
authors.lastname: Barnholtz-Sloan
authors.affiliation: Center for Proteomics and Bioinformatics.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Chance
authors.affiliation: Division of Infectious Diseases and HIV Medicine.
authors.forename: Scott F
authors.initials: SF
authors.lastname: Sieg
keywords: ART; CMTC; HIV; SRM; proteomics