2. Academic Validation
  3. AKT Signaling Modulates Latent Viral Reservoir Viability in HIV-1-Infected Blood-Brain Barrier Pericytes

AKT Signaling Modulates Latent Viral Reservoir Viability in HIV-1-Infected Blood-Brain Barrier Pericytes

  • J Biol Chem. 2023 Dec 1:105526. doi: 10.1016/j.jbc.2023.105526.
Oandy Naranjo 1,  Silvia Torices 2,  Paul R Clifford 2,  Thaidy Rodriguez 3,  Olivia M Osborne 2,  Destiny Tiburcio 2,  Nikolai Fattakhov 2,  Minseon Park 2,  Mario Stevenson 4,  Michal Toborek 5
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA. Electronic address: oxn62@miami.edu.
  • 2 Department of Biochemistry and Molecular Biology, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA.
  • 3 Department of Urology, University of California San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • 4 Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA.
  • 5 Department of Biochemistry and Molecular Biology, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA. Electronic address: mtoborek@med.miami.edu.
PMID: 38043797 DOI: 10.1016/j.jbc.2023.105526
Abstract

Despite antiretroviral therapy (ART), chronic forms of HIV-associated neurocognitive disorders (HAND) affect an estimated 50% of individuals living with HIV, greatly impacting their quality of life. The prevailing theory of HAND progression posits that chronic inflammation arising from the activation of latent viral reservoirs leads to progressive damage in the central nervous system (CNS). Recent evidence indicates that blood-brain barrier (BBB) pericytes are capable of active HIV-1 infection; however, their latent Infection has not been defined. Given their location and function, BBB pericytes are poised to be a key viral reservoir in the development of HAND. We present the first transcriptional analysis of uninfected, active, and latent human BBB pericytes, revealing distinct transcriptional phenotypes. In addition, we demonstrate that latent Infection of BBB pericytes relies on Akt signaling for reservoir survival. These findings provide insight into the state of reservoir maintenance in the CNS during HIV-1 Infection and provide novel targets for reservoir clearance.

Keywords

Human immunodeficiency virus (HIV); Vascular Biology; estrogen receptor.; neurochemistry; neurodegeneration.

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