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

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• The latent HIV cell reservoir poses a significant barrier to complete viral eradication.
• Understanding the molecular characteristics of latently infected cells is crucial for developing targeted therapies.

Purpose of the Study:

• To comprehensively profile latently HIV-infected T cells at the protein and RNA levels.
• To identify novel molecular biomarkers for the selective enrichment of these cells.

Main Methods:

• Isobaric labeling quantitative proteomics and RNA sequencing were employed for molecular profiling.
• Integrated data analysis was used for biomarker selection.
• Flow cytometry and HIV integrant assay were used to monitor cell enrichment.

Main Results:

• 1453 proteins and 618 genes were found to be significantly altered in latently infected cells.
• Antibodies targeting CEACAM1 and PLXNB2 enriched latently infected cells by an average of 5.8-fold.
• The enrichment levels were comparable to previously reported biomarkers.

Conclusions:

• CEACAM1 and PLXNB2 represent promising biomarkers for targeting the latent HIV reservoir.
• Individual biomarkers likely identify subsets of latently infected cells.
• An extended antibody panel may be necessary for comprehensive reservoir targeting.