Circulating levels of ATP is a biomarker of HIV cognitive impairment.

Stephani Velasquez,Mikhail Golovko,Anna Maria Gorska,Nabab Khan,Silvana Valdebenito,Jonathan Geiger,Eliseo A Eugenin,Lisa Prevedel

doi:10.1016/j.ebiom.2019.10.029

Stephani Velasquez, Mikhail Golovko + Show 6 more

Open Access

https://doi.org/10.1016/j.ebiom.2019.10.029

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Abstract

BackgroundIn developed countries, Human Immunodeficiency Virus type-1 (HIV-1) infection has become a chronic disease despite the positive effects of anti-retroviral therapies (ART), but still at least half of the HIV infected population shown signs of cognitive impairment. Therefore, biomarkers of HIV cognitive decline are urgently needed.MethodsWe analyze the opening of one of the larger channels expressed by humans, pannexin-1 (Panx-1) channels, in the uninfected and HIV infected population (n = 175). We determined channel opening and secretion of intracellular second messengers released through the channel such as PGE2 and ATP. Also, we correlated the opening of Panx-1 channels with the circulating levels of PGE2 and ATP as well as cogntive status of the individuals analyzed.FindingsHere, we demonstrate that Panx-1 channels on fresh PBMCs obtained from uninfected individuals are closed and no significant amounts of PGE2 and ATP are detected in the circulation. In contrast, in all HIV-infected individuals analyzed, even the ones under effective ART, a spontaneous opening of Panx-1 channels and increased circulating levels of PGE2 and ATP were detected. Circulating levels of ATP were correlated with cognitive decline in the HIV-infected population supporting that ATP is a biomarker of cognitive disease in the HIV-infected population.InterpretationWe propose that circulating levels of ATP could predict CNS compromise and lead to the breakthroughs necessary to detect and prevent brain compromise in the HIV-infected population.

Highlights

The pathogenesis of HIV-infected individuals (HIV)-infection involves a series of dynamic interactions between HIV and several host proteins to support effective HIV-infection, replication, generation of viral reservoirs, and associated inflammation [1,2,3]
The HIV-positive cohort had an average of 15.9 ± 6.8 years of living with HIV, an average CD4 count of 323.2 ± 285.7 cells/μl, and mean plasma HIV RNA of
Among the HIV-positive participants, 69% had some degree of cognitive impairment, as determined by neuropsychological testing (Table 1)

Summary

Introduction

The pathogenesis of HIV-infection involves a series of dynamic interactions between HIV and several host proteins to support effective HIV-infection, replication, generation of viral reservoirs, and associated inflammation [1,2,3]. Despite effective antiretroviral therapy (ART), most HIV-infected individuals still showed strong evidence of chronic systemic and brain inflammation resulting in cognitive impairment. Pannexin-1 proteins form a large plasma membrane channel that, upon opening, allows the release of several intracellular mediators, including ATP and other nucleotides, prostaglandins, glutamate, NAD+, and metabolites such as glucose. In physiological conditions, these channels remain closed. Human Immunodeficiency Virus type-1 (HIV-1) infection has become a chronic disease despite the positive effects of anti-retroviral therapies (ART), but still at least half of the HIV infected population shown signs of cognitive impairment.

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