{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T02:47:36Z","timestamp":1788058056274,"version":"build-2784847793"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>The widespread use of combination antiretroviral therapy (cART) has led to the accelerated aging of the HIV-infected population, and these patients continue to have a range of mild to moderate HIV-associated neurocognitive disorders (HAND). Infection results in altered mitochondrial function. The HIV-1 viral protein Tat significantly alters mtDNA content and enhances oxidative stress in immune cells. Microglia are the immune cells of the central nervous system (CNS) that exhibit a significant mitotic potential and are thus susceptible to telomere shortening. HIV disrupts the normal interplay between microglia and neurons, thereby inducing neurodegeneration. HIV cART contributes to the inhibition of telomerase activity and premature telomere shortening in activated peripheral blood mononuclear cells (PBMC). However, limited information is available on the effect of cART on telomere length (TL) in microglia. Although it is well established that telomere shortening induces cell senescence and contributes to the development of age-related neuro-pathologies, the effect of HIV-Tat on telomere length in human microglial cells and its potential contribution to HAND are not well understood. It is speculated that in HAND intrinsic molecular mechanisms that control energy production underlie microglia-mediated neuronal injury. TL, telomerase and mtDNA expression were quantified in microglial cells using real time PCR. Cellular energetics were measured using the Seahorse assay. The changes in mitochondrial function were examined by Raman Spectroscopy. We have also examined TL in the PBMC obtained from HIV-1 infected rapid progressors (RP) on cART and those who were cART na\u00efve, and observed a significant decrease in telomere length in RP on cART as compared to RP\u2019s who were cART na\u00efve. We observed a significant decrease in telomerase activity, telomere length and mitochondrial function, and an increase in oxidative stress in human microglial cells treated with HIV Tat. Neurocognitive impairment in HIV disease may in part be due to accelerated neuro-pathogenesis in microglial cells, which is attributable to increased oxidative stress and mitochondrial dysfunction.<\/jats:p>","DOI":"10.3390\/vaccines9070721","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T12:03:27Z","timestamp":1625141007000},"page":"721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Telomere Length Shortening in Microglia: Implication for Accelerated Senescence and Neurocognitive Deficits in HIV"],"prefix":"10.3390","volume":"9","author":[{"given":"Chiu-Bin","family":"Hsiao","sequence":"first","affiliation":[{"name":"Medicine Institute, School of Medicine, Infectious Diseases, Drexel University, Positive Health Clinic, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA 15212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harneet","family":"Bedi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Immunology & Rheumatology, University at Buffalo\u2019s Clinical Translational Research Center, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Gomez","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Immunology & Rheumatology, University at Buffalo\u2019s Clinical Translational Research Center, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayesha","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Immunology & Rheumatology, University at Buffalo\u2019s Clinical Translational Research Center, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Meciszewski","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Immunology & Rheumatology, University at Buffalo\u2019s Clinical Translational Research Center, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravikumar","family":"Aalinkeel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Immunology & Rheumatology, University at Buffalo\u2019s Clinical Translational Research Center, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting Chean","family":"Khoo","sequence":"additional","affiliation":[{"name":"Department of Physics, University at Albany SUNY, Albany, NY 12222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna V.","family":"Sharikova","sequence":"additional","affiliation":[{"name":"Department of Physics, University at Albany SUNY, Albany, NY 12222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Khmaladze","sequence":"additional","affiliation":[{"name":"Department of Physics, University at Albany SUNY, Albany, NY 12222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supriya D.","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Immunology & Rheumatology, University at Buffalo\u2019s Clinical Translational Research Center, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,1]]},"reference":[{"key":"ref_1","first-page":"137","article-title":"Transcription of HIV: Tat and Cellular Chromatin","volume":"55","author":"Gatignol","year":"2007","journal-title":"Charact. 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