Circulating Levels of ATP is a Biomarker of HIV Cognitive Impairment

Overview

Journal EBioMedicine

Specialty Biomedical Engineering

Date 2019 Dec 7

PMID 31806564

Citations 27

Authors

Stephani Velasquez

Lisa Prevedel

Silvana Valdebenito

Anna Maria Gorska

Mikhail Golovko

Nabab Khan

Jonathan Geiger

Eliseo A Eugenin

Affiliations

Soon will be listed here.

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 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.

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References

Seror C, Melki M, Subra F, Raza S, Bras M, Saidi H . Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection. J Exp Med. 2011; 208(9):1823-34. PMC: 3171090. DOI: 10.1084/jem.20101805. View

Shapiro M, Jellinek M, Pyrros D, Sundine M, Baue A . Clearance and maintenance of blood nucleotide levels with adenosine triphosphate-magnesium chloride injection. Circ Shock. 1992; 36(1):62-7. View

Elliott M, Chekeni F, Trampont P, Lazarowski E, Kadl A, Walk S . Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature. 2009; 461(7261):282-6. PMC: 2851546. DOI: 10.1038/nature08296. View

Yi Z, Xie L, Zhou C, Yuan H, Ouyang S, Fang Z . P2Y receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2',3'-dideoxycytidine. Purinergic Signal. 2017; 14(1):47-58. PMC: 5842155. DOI: 10.1007/s11302-017-9594-z. View

Barat C, Proust A, Deshiere A, Leboeuf M, Drouin J, Tremblay M . Astrocytes sustain long-term productive HIV-1 infection without establishment of reactivable viral latency. Glia. 2018; 66(7):1363-1381. DOI: 10.1002/glia.23310. View

Kurtenbach S, Prochnow N, Kurtenbach S, Klooster J, Zoidl C, Dermietzel R . Pannexin1 channel proteins in the zebrafish retina have shared and unique properties. PLoS One. 2013; 8(10):e77722. PMC: 3808535. DOI: 10.1371/journal.pone.0077722. View

Laubenberger J, Haussinger D, Bayer S, Thielemann S, Schneider B, Mundinger A . HIV-related metabolic abnormalities in the brain: depiction with proton MR spectroscopy with short echo times. Radiology. 1996; 199(3):805-10. DOI: 10.1148/radiology.199.3.8638009. View

Antonioli L, Colucci R, Pellegrini C, Giustarini G, Tuccori M, Blandizzi C . The role of purinergic pathways in the pathophysiology of gut diseases: pharmacological modulation and potential therapeutic applications. Pharmacol Ther. 2013; 139(2):157-88. DOI: 10.1016/j.pharmthera.2013.04.002. View

Wright P, Vaida F, Fernandez-de Thomas R, Rutlin J, Price R, Lee E . Cerebral white matter integrity during primary HIV infection. AIDS. 2014; 29(4):433-42. PMC: 4916955. DOI: 10.1097/QAD.0000000000000560. View

10.

Orellana J, Velasquez S, Williams D, Saez J, Berman J, Eugenin E . Pannexin1 hemichannels are critical for HIV infection of human primary CD4+ T lymphocytes. J Leukoc Biol. 2013; 94(3):399-407. PMC: 3747122. DOI: 10.1189/jlb.0512249. View

11.

McLaurin K, Li H, Booze R, Mactutus C . Disruption of Timing: NeuroHIV Progression in the Post-cART Era. Sci Rep. 2019; 9(1):827. PMC: 6351586. DOI: 10.1038/s41598-018-36822-1. View

12.

Rezer J, Adefegha S, Ecker A, Passos D, Saccol R, Bertoldo T . Changes in inflammatory/cardiac markers of HIV positive patients. Microb Pathog. 2017; 114:264-268. DOI: 10.1016/j.micpath.2017.11.045. View

13.

Woods S, Rippeth J, Frol A, Levy J, Ryan E, Soukup V . Interrater reliability of clinical ratings and neurocognitive diagnoses in HIV. J Clin Exp Neuropsychol. 2004; 26(6):759-78. DOI: 10.1080/13803390490509565. View

14.

Bairwa D, Kumar V, Vyas S, Das B, Srivastava A, Pandey R . Case control study: magnetic resonance spectroscopy of brain in HIV infected patients. BMC Neurol. 2016; 16:99. PMC: 4942893. DOI: 10.1186/s12883-016-0628-x. View

15.

Walker B, Yu X . Unravelling the mechanisms of durable control of HIV-1. Nat Rev Immunol. 2013; 13(7):487-98. DOI: 10.1038/nri3478. View

16.

Chekeni F, Elliott M, Sandilos J, Walk S, Kinchen J, Lazarowski E . Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis. Nature. 2010; 467(7317):863-7. PMC: 3006164. DOI: 10.1038/nature09413. View

17.

van Zoest R, Underwood J, De Francesco D, Sabin C, Cole J, Wit F . Structural Brain Abnormalities in Successfully Treated HIV Infection: Associations With Disease and Cerebrospinal Fluid Biomarkers. J Infect Dis. 2017; 217(1):69-81. DOI: 10.1093/infdis/jix553. View

18.

Hermansson L, Yilmaz A, Axelsson M, Blennow K, Fuchs D, Hagberg L . Cerebrospinal fluid levels of glial marker YKL-40 strongly associated with axonal injury in HIV infection. J Neuroinflammation. 2019; 16(1):16. PMC: 6345016. DOI: 10.1186/s12974-019-1404-9. View

19.

Celetti S, Cowan K, Penuela S, Shao Q, Churko J, Laird D . Implications of pannexin 1 and pannexin 3 for keratinocyte differentiation. J Cell Sci. 2010; 123(Pt 8):1363-72. DOI: 10.1242/jcs.056093. View

20.

Locovei S, Bao L, Dahl G . Pannexin 1 in erythrocytes: function without a gap. Proc Natl Acad Sci U S A. 2006; 103(20):7655-9. PMC: 1472500. DOI: 10.1073/pnas.0601037103. View