Retinoic Acid Improves the Recovery of Replication-Competent Virus from Latent SIV Infected Cells

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Accurate estimation and eradication of Human Immunodeficiency Virus (HIV) viral reservoirs are hindered by incomplete reactivation of latent virus.
• Current methods for detecting latent HIV struggle to fully activate cells harboring the virus.

Purpose of the Study:

• To investigate if retinoic acid (RA) enhances in vitro and in vivo virus replication and improves the detection of latent HIV reservoirs.
• To assess RA's efficacy in augmenting viral reactivation for more accurate reservoir quantification.

Main Methods:

• Peripheral blood mononuclear cells (PBMCs) from SIV-infected rhesus macaques (RMs) were cultured with or without RA.
• Viral RNA and p27 levels were quantified using RT-qPCR and ELISA.
• Latent viral reservoirs were estimated using Tat/Rev-Induced Limited Dilution Assay (TILDA) and Quantitative Viral Outgrowth Assay (QVOA).

Main Results:

• Retinoic acid (RA) increased viral replication in both in vitro and in vivo conditions.
• RA augmented reactivation of the replication-competent viral reservoir in ART-suppressed RMs, showing a >2.3-fold increase with QVOA and 1-2 fold increments with TILDA.
• Flow cytometry revealed RA elicited broad CD4 T-cell activation, improving reservoir assay estimates.

Conclusions:

• Retinoic acid (RA) can enhance the efficiency of current protocols for in vitro and potentially in vivo estimates of CD4+ T cell latent reservoirs.
• RA's ability to broadly activate CD4 T-cells makes it a valuable tool for improving viral reservoir detection and potentially aiding HIV eradication strategies.