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

Authors

Sausan Azzam, Case Western Reserve UniversityFollow
Daniela M. Schlatzer, Case Western Reserve UniversityFollow
Sean Maxwell, Case Western Reserve UniversityFollow
Xiaolin Li, Case Western Reserve UniversityFollow
Douglas Bazdar, Case Western Reserve UniversityFollow
Yanwen Chen, Case Western Reserve University
Robert Asaad, Case Western Reserve University
Jill S. Barnholtz-Sloan, Case Western Reserve University
Mark R. Chance, Case Western Reserve UniversityFollow
Scott F. Sieg, Case Western Reserve UniversityFollow

Author ORCID Identifier

Jill S. Barnholtz-Sloan

Mark R. Chance

Document Type

Article

Publication Date

3-15-2016

DOI

10.1093/ofid/ofw037

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.

Keywords

ART, CMTC, HIV, proteomics, SRM

Publication Title

Open Forum Infectious Diseases

Volume

3

Issue

2

Rights

© The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Sausan Azzam and others, 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, Open Forum Infectious Diseases, Volume 3, Issue 2, Spring 2016, ofw037, https://doi.org/10.1093/ofid/ofw037