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Integrated Proteomics and Transcriptomics Analyses Identify Novel Cell Surface Markers of HIV Latency

Overview
Journal Virology
Specialty Microbiology
Date 2022 Jun 17
PMID 35714458
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Abstract

Elimination of the latent HIV cell reservoir may be possible, if the molecular identity of latently infected cells were fully elucidated. We conducted comprehensive molecular profiling, at the protein and RNA levels, of primary T cells latently infected with HIV in vitro. Isobaric labelling quantitative proteomics and RNA sequencing identified 1453 proteins and 618 genes, altered in latently infected cells compared to mock-infected controls (p < 0.05). Biomarker selection was based on results from integrated data analysis. Relative enrichment for latently infected cells was monitored using flow cytometric sorting and the HIV integrant assay. Antibodies against selected proteins, encoded by CEACAM1 and PLXNB2, enabled enrichment of latently infected cells from cell mixtures by 3-10 fold (5.8 average, p < 0.001), comparable to levels obtained with biomarkers reported previously. Individual biomarkers are likely linked to subsets of latently infected cells, and an extended antibody panel will be required to inclusively target the latent HIV reservoir.

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References
1.
Iglesias-Ussel M, Vandergeeten C, Marchionni L, Chomont N, Romerio F . High levels of CD2 expression identify HIV-1 latently infected resting memory CD4+ T cells in virally suppressed subjects. J Virol. 2013; 87(16):9148-58. PMC: 3754042. DOI: 10.1128/JVI.01297-13. View

2.
Wong J, Hezareh M, Gunthard H, Havlir D, Ignacio C, Spina C . Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science. 1997; 278(5341):1291-5. DOI: 10.1126/science.278.5341.1291. View

3.
Descours B, Petitjean G, Lopez-Zaragoza J, Bruel T, Raffel R, Psomas C . CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses. Nature. 2017; 543(7646):564-567. DOI: 10.1038/nature21710. View

4.
Rawlings S, Alonzo 3rd F, Kozhaya L, Torres V, Unutmaz D . Elimination of HIV-1-Infected Primary T Cell Reservoirs in an In Vitro Model of Latency. PLoS One. 2015; 10(5):e0126917. PMC: 4437782. DOI: 10.1371/journal.pone.0126917. View

5.
Beliakova-Bethell N, Mukim A, White C, Deshmukh S, Abewe H, Richman D . Histone deacetylase inhibitors induce complex host responses that contribute to differential potencies of these compounds in HIV reactivation. J Biol Chem. 2019; 294(14):5576-5589. PMC: 6462528. DOI: 10.1074/jbc.RA118.005185. View