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

Highlights: • Elimination of latently infected cells is necessary to cure HIV-1 infection. • SWATH mass spectrometry was used to identify biomarkers of HIV-1 latency using a cell line T cell model. • Several candidates were validated in multiple latently infected cell lines. • Expression of candidates was variable across latent cells, indicating broad detection will require a multiplex method. 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.