Discovery of candidate HIV-1 latency biomarkers using an OMICs approach

Michael Belshan; Alexander Holbrook; Joseph W George; Hannah E Durant; Michael Callahan 2nd; Spencer Jaquet; John T West; Jacob Siedlik; Pawel Ciborowski

doi:10.1016/j.virol.2021.03.003

Discovery of candidate HIV-1 latency biomarkers using an OMICs approach

Virology. 2021 Jun:558:86-95. doi: 10.1016/j.virol.2021.03.003. Epub 2021 Mar 11.

Authors

Michael Belshan¹, Alexander Holbrook², Joseph W George², Hannah E Durant², Michael Callahan 2nd², Spencer Jaquet³, John T West⁴, Jacob Siedlik⁵, Pawel Ciborowski³

Affiliations

¹ Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE, USA. Electronic address: michaelbelshan@creighton.edu.
² Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE, USA.
³ Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
⁴ Department of Biochemistry, And the Nebraska Center for Virology, University of Nebraska, Lincoln, NE, USA.
⁵ Department of Exercise Science and Pre-Health Professions, Creighton University, Omaha, NE, USA.

Abstract

Infection with HIV-1 remains uncurable due to reservoirs of latently infected cells. Any potential cure for HIV will require a mechanism to identify and target these cells in vivo. We created a panel of Jurkat cell lines latently infected with the HIV DuoFlo virus to identify candidate biomarkers of latency. SWATH mass spectrometry was used to compare the membrane proteomes of one of the cell lines to parental Jurkat cells. Several candidate proteins with significantly altered expression were identified. The differential expression of several candidates was validated in multiple latently infected cell lines. Three factors (LAG-3, CD147,CD231) were altered across numerous cell lines, but the expression of most candidate biomarkers was variable. These results confirm that phenotypic differences in latently infected cells exists and identify additional novel biomarkers. The variable expression of biomarkers across different cell clones suggests universal antigen-based detection of latently infected cells may require a multiplex approach.

Keywords: Biomarker discovery; HIV; Latency; Proteomics; SWATH-MS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers / analysis
Cell Line
HIV-1 / chemistry*
HIV-1 / genetics*
Humans
Jurkat Cells
Mass Spectrometry / methods
Proteomics / methods*
T-Lymphocytes / virology*
U937 Cells
Virus Latency*

Substances

Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding