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Author Notes:

Neil Sidell, Email: nsidell@emory.edu ; Maureen A. Kane, Email: mkane@rx.umaryland.edu

Both authors listed have made a substantial, direct, and intellectual contribution to the review. All authors have read and agreed to the published version of the manuscript.

The authors sincerely thank Aftab A. Ansari and R. Keith Reeves for many fruitful discussions and constructive ideas during the course of our studies of retinoids and HIV/SIV and for their help in the final reading and preparation of this manuscript. We also thank Siddappa Byrareddy for sharing his ideas and data relating to RA and re-activation of replication-competent SIV reservoirs. Additionally, we are grateful to William T. Andrews for the artistic rendering of Figure 8.

The authors declare no conflict of interest.

Subjects:

Research Funding:

This project has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract no. HHSN272201000046C and HHSN272201500013I; National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development grant no. R01HD077260. Additional support was provided by the University of Maryland School of Pharmacy Mass Spectrometry Center (SOP1841-IQB2014). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the funders.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Nutrition & Dietetics
  • retinoic acid
  • HIV
  • mucosal immunity
  • retinoids
  • immune regulation
  • INNATE LYMPHOID-CELLS
  • NATURAL-KILLER-CELLS
  • INTESTINAL DENDRITIC CELLS
  • TRANSCRIPTION FACTOR GATA3
  • NONHUMAN PRIMATE MODEL
  • REGULATORY T-CELLS
  • VITAMIN-A
  • RHESUS MACAQUES
  • INTEGRIN ALPHA(4)BETA(7)
  • EXPRESSION

Actions of Retinoic Acid in the Pathophysiology of HIV Infection

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Journal Title:

NUTRIENTS

Volume:

Volume 14, Number 8

Publisher:

Type of Work:

Article | Final Publisher PDF

Abstract:

The vitamin A metabolite all-trans retinoic acid (RA) plays a key role in tissue homeostasis and mucosal immunity. RA is produced by gut-associated dendritic cells, which are among the first cells encountered by HIV. Acute HIV infection results in rapid reduction of RA levels and dysregulation of immune cell populations whose identities and function are largely controlled by RA. Here, we discuss the potential link between the roles played by RA in shaping intestinal immune responses and the manifestations and pathogenesis of HIV-associated enteropathy and similar conditions observed in SIV-infected non-human primate models. We also present data demonstrating the ability of RA to enhance the activation of replication-competent viral reservoirs from subjects on suppressive anti-retroviral therapy. The data suggest that retinoid supplementation may be a useful adjuvant for countering the pathologic condition of the gastro-intestinal tract associated with HIV infection and as part of a strategy for reactivating viral reservoirs as a means of depleting latent viral infection.

Copyright information:

© 2022 by the authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/rdf).
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