Circulating levels of ATP is a biomarker of HIV cognitive impairment

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

Research output: Contribution to journalArticle

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Abstract

Background: In 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. Methods: We 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. Findings: Here, 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. Interpretation: We 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.

Original languageEnglish (US)
Article number102503
JournalEBioMedicine
Volume51
DOIs
StatePublished - Jan 2020

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Keywords

  • Anti-retroviral/dementia/HIV-1 reservoirs/NeuroHIV/Pannexin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Velasquez, S., Prevedel, L., Valdebenito, S., Gorska, A. M., Golovko, M., Khan, N., Geiger, J., & Eugenin, E. A. (2020). Circulating levels of ATP is a biomarker of HIV cognitive impairment. EBioMedicine, 51, [102503]. https://doi.org/10.1016/j.ebiom.2019.10.029