AKT signaling modulates latent viral reservoir viability in HIV-1-infected blood-brain barrier pericytes.

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.

Pericyte infection by HIV-1: a fatal attraction.

While HIV-1 is primarily an infection of CD4 + T cells, there is an emerging interest towards understanding how infection of other cell types can contribute to HIV-associated comorbidities. For HIV-1 to cross from the blood stream into tissues, the virus must come in direct contact with the vascular endothelium, including pericytes that envelope vascular endothelial cells. Pericytes are multifunctional cells that have been recognized for their essential role in angiogenesis, vessel maintenance, and blood flow rate. Most importantly, recent evidence has shown that pericytes can be a target of HIV-1 infection and support an active stage of the viral life cycle, with latency also suggested by in vitro data. Pericyte infection by HIV-1 has been confirmed in the postmortem human brains and in lungs from SIV-infected macaques. Moreover, pericyte dysfunction has been implicated in a variety of pathologies ranging from ischemic stroke to diabetes, which are common comorbidities among people with HIV-1. In this review, we discuss the role of pericytes during HIV-1 infection and their contribution to the progression of HIV-associated comorbidities.