Integrated proteomics and transcriptomics analyses identify novel cell surface markers of HIV latency

Virology. 2022 Aug:573:50-58. doi: 10.1016/j.virol.2022.06.003. Epub 2022 Jun 4.

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.

Keywords: Biomarkers; CEACAM1; HIV latency; PLXNB2; Primary CD4(+) T cells; Proteome; Quantitative proteomics; RNA-Seq; Transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • CD4-Positive T-Lymphocytes
  • HIV Infections*
  • HIV-1* / genetics
  • Humans
  • Proteomics
  • Transcriptome
  • Virus Activation
  • Virus Latency