Date Published:
2020 Jan

Publication Type:
Journal Article

Authors:

S. Velasquez
L. Prevedel
S. Valdebenito
A.Maria Gorska
M. Golovko
N. Khan
J. Geiger
E.A. Eugenin

Secondary:
EBioMedicine

Volume:
51

Pagination:
102503

PMID:
31806564

URL:
https://pubmed.ncbi.nlm.nih.gov/31806564

DOI:
10.1016/j.ebiom.2019.10.029

Keywords:
Adenosine Triphosphate;Adult;Aged;Biomarkers;Blood-Brain Barrier;Cognitive Dysfunction;Connexins;Dinoprostone;External;Female;HIV Infections;Humans;Inflammation Mediators;Ion Channel Gating;Leukocytes, Mononuclear;Male;Middle Aged;Nerve Tissue Proteins;Transendothelial and Transepithelial Migration

Abstract:
<p>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 PGE and ATP. Also, we correlated the opening of Panx-1 channels with the circulating levels of PGE 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 PGE 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 PGE 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.</p>