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Cholesterol Metabolism in Antigen-Presenting Cells and HIV-1 Trans-Infection of CD4+ T Cells

Daniel Okpaise1, Nicolas Sluis-Cremer1, Giovanna Rappocciolo1

  • 1Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

Viruses
|December 23, 2023
PubMed

Insights

Non-progressing HIV-1 patients prevent viral spread through altered cholesterol metabolism in their cells. This cellular mechanism blocks HIV-1 trans-infection, offering insights into potential cures.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Antiretroviral therapy (ART) manages HIV-1 but cannot eliminate the latent viral reservoir.
  • Latent HIV-1 persists in resting CD4+ T cells, posing a barrier to a cure.
  • Intercellular HIV-1 transfer (trans-infection) from antigen-presenting cells (APCs) to CD4+ T cells establishes this reservoir and is ART-resistant.

Approach:

  • This review examines the unique characteristic of HIV-1-positive non-progressors (NPs) who control infection without ART.
  • The focus is on the proposed genetically inherited, altered cholesterol metabolism in the APCs of NPs.
  • The role of cellular cholesterol homeostasis and efflux in preventing HIV-1 trans-infection in NPs is investigated.

Key Points:

  • APCs from NPs do not trans-infect CD4+ T cells, unlike those from typical HIV-1 patients.
  • Altered cholesterol metabolism in NP APCs is hypothesized to be the driving force behind this protective mechanism.
  • Cholesterol efflux from APCs is identified as a critical factor in blocking HIV-1 trans-infection.

Conclusions:

  • Understanding the link between cholesterol metabolism and HIV-1 trans-infection in NPs is crucial for developing a functional HIV-1 cure.
  • Targeting cholesterol pathways may offer novel therapeutic strategies to clear the latent HIV-1 reservoir.
  • The findings highlight the potential of host-intrinsic factors in controlling viral persistence.

Keywords:
HIV-1antigen-presenting cellsantiretroviral therapycholesterol metabolismimmunometabolismlatent reservoirnon-progressortrans-infection

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