TY - JOUR
T1 - Circulating levels of ATP is a biomarker of HIV cognitive impairment
AU - Velasquez, Stephani
AU - Prevedel, Lisa
AU - Valdebenito, Silvana
AU - Gorska, Anna Maria
AU - Golovko, Mikhail
AU - Khan, Nabab
AU - Geiger, Jonathan
AU - Eugenin, Eliseo A.
N1 - Funding Information:
All NNTC related funding provides a unique human repository for research purposes www.nntc.org. The Alfred P. Sloan Foundation Minority fellowship provides funds to Dr. Velasquez during her Ph.D. training. Funding for J.D.G. provided resources to perform serum analysis in University of North Dakota for ATP, ADP, AMP, and Adenosine. The major funding sources were The National Institute of Mental Health grant, MH096625, the National Institute of Neurological Disorders and Stroke, NS105584, and UTMB internal funding (to E.A.E).The main responsible investigator that has full access to all data and the final responsibility of publication is Dr. Eugenin. None of the funders have any participation in data collection, data analysis, interpretation or writing this report.We would like to thank National NeuroAIDS Tissue Consortium (NNTC) for providing all human samples. The NNTC is made possible through funding from the NIMH and NINDS by the following grants: Manhattan HIV Brain Bank (MHBB): U24MH100931; Texas NeuroAIDS Research Center (TNRC): U24MH100930; National Neurological AIDS Bank (NNAB): U24MH100929; California NeuroAIDS Tissue Network (CNTN): U24MH100928; and Data Coordinating Center (DCC): U24MH100925. We want to thank the New Jersey and New York Blood Center, the Alfred P. Sloan Foundation Minority fellowship (to S.V.), and Mount Sinai NeuroAIDS Disparities Summer Institute, R25 MH080663 (to S.V. trainee). This work was funded by The National Institute of Mental Health grant, MH096625, the National Institute of Neurological Disorders and Stroke, NS105584, and UTMB internal funding (to E.A.E). Research in the Geiger (J.D.G.) laboratory was supported by the National Institute of General Medical Sciences under award numbers P30GM100329 and U54GM115458, the National Institute of Mental Health under award numbers R01MH100972 and R01MH105329, the National Institute of Neurological Diseases and Stroke under award number R01NS065957, and the National Institute of Drug Abuse under award number 2R01DA032444.
Funding Information:
All NNTC related funding provides a unique human repository for research purposes www.nntc.org . The Alfred P. Sloan Foundation Minority fellowship provides funds to Dr. Velasquez during her Ph.D. training. Funding for J.D.G. provided resources to perform serum analysis in University of North Dakota for ATP, ADP, AMP, and Adenosine. The major funding sources were The National Institute of Mental Health grant, MH096625 , the National Institute of Neurological Disorders and Stroke , NS105584 , and UTMB internal funding (to E.A.E).The main responsible investigator that has full access to all data and the final responsibility of publication is Dr. Eugenin. None of the funders have any participation in data collection, data analysis, interpretation or writing this report. 6
Funding Information:
We would like to thank National NeuroAIDS Tissue Consortium (NNTC) for providing all human samples. The NNTC is made possible through funding from the NIMH and NINDS by the following grants: Manhattan HIV Brain Bank (MHBB): U24MH100931 ; Texas NeuroAIDS Research Center (TNRC): U24MH100930 ; National Neurological AIDS Bank (NNAB): U24MH100929 ; California NeuroAIDS Tissue Network (CNTN): U24MH100928 ; and Data Coordinating Center (DCC): U24MH100925 . We want to thank the New Jersey and New York Blood Center, the Alfred P. Sloan Foundation Minority fellowship (to S.V.), and Mount Sinai NeuroAIDS Disparities Summer Institute , R25 MH080663 (to S.V. trainee). This work was funded by The National Institute of Mental Health grant, MH096625 , the National Institute of Neurological Disorders and Stroke , NS105584 , and UTMB internal funding (to E.A.E). Research in the Geiger (J.D.G.) laboratory was supported by the National Institute of General Medical Sciences under award numbers P30GM100329 and U54GM115458 , the National Institute of Mental Health under award numbers R01MH100972 and R01MH105329 , the National Institute of Neurological Diseases and Stroke under award number R01NS065957 , and the National Institute of Drug Abuse under award number 2R01DA032444 .
Publisher Copyright:
© 2019 The Authors
PY - 2020/1
Y1 - 2020/1
N2 - 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.
AB - 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.
KW - Anti-retroviral/dementia/HIV-1 reservoirs/NeuroHIV/Pannexin
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U2 - 10.1016/j.ebiom.2019.10.029
DO - 10.1016/j.ebiom.2019.10.029
M3 - Article
C2 - 31806564
AN - SCOPUS:85075530239
SN - 2352-3964
VL - 51
JO - EBioMedicine
JF - EBioMedicine
M1 - 102503
ER -