Anti-HIV Drugs Cause Mitochondrial Dysfunction in Monocyte-Derived Macrophages

Combination antiretroviral therapy (cART) dramatically changed the face of the HIV/AIDS pandemic, making it one of the most prominent medical breakthroughs of the past 3 decades. However, as the life span of persons living with HIV (PLWH) continues to approach that of the general population, the sam...

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Autores principales: Wallace, Jennillee, Gonzalez, Hemil, Rajan, Reshma, Narasipura, Srinivas D., Virdi, Amber K., Olali, Arnold Z., Naqib, Ankur, Arbieva, Zarema, Maienschein-Cline, Mark, Al-Harthi, Lena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9017340/
https://www.ncbi.nlm.nih.gov/pubmed/35293780
http://dx.doi.org/10.1128/aac.01941-21
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author Wallace, Jennillee
Gonzalez, Hemil
Rajan, Reshma
Narasipura, Srinivas D.
Virdi, Amber K.
Olali, Arnold Z.
Naqib, Ankur
Arbieva, Zarema
Maienschein-Cline, Mark
Al-Harthi, Lena
author_facet Wallace, Jennillee
Gonzalez, Hemil
Rajan, Reshma
Narasipura, Srinivas D.
Virdi, Amber K.
Olali, Arnold Z.
Naqib, Ankur
Arbieva, Zarema
Maienschein-Cline, Mark
Al-Harthi, Lena
author_sort Wallace, Jennillee
collection PubMed
description Combination antiretroviral therapy (cART) dramatically changed the face of the HIV/AIDS pandemic, making it one of the most prominent medical breakthroughs of the past 3 decades. However, as the life span of persons living with HIV (PLWH) continues to approach that of the general population, the same cannot be said regarding their quality of life. PLWH are affected by comorbid conditions such as high blood pressure, diabetes, and neurocognitive impairment at a higher rate and increased severity than their age-matched counterparts. PLWH also have higher levels of inflammation, the drivers of which are not entirely clear. As cART treatment is lifelong, we assessed here the effects of cART, independent of HIV, on primary human monocyte-derived macrophages (MDMs). MDMs were unskewed or skewed to an alternative phenotype and treated with Atripla or Triumeq, two first-line cART treatments. We report that Triumeq skewed alternative MDMs toward an inflammatory nonsenescent phenotype. Both Atripla and Triumeq caused mitochondrial dysfunction, specifically efavirenz and abacavir. Additionally, transcriptome sequencing (RNA-seq) demonstrated that both Atripla and Triumeq caused differential regulation of genes involved in immune regulation and cell cycle and DNA repair. Collectively, our data demonstrate that cART, independent of HIV, alters the MDM phenotype. This suggests that cART may contribute to cell dysregulation in PLWH that subsequently results in increased susceptibility to comorbidities.
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spelling pubmed-90173402022-04-20 Anti-HIV Drugs Cause Mitochondrial Dysfunction in Monocyte-Derived Macrophages Wallace, Jennillee Gonzalez, Hemil Rajan, Reshma Narasipura, Srinivas D. Virdi, Amber K. Olali, Arnold Z. Naqib, Ankur Arbieva, Zarema Maienschein-Cline, Mark Al-Harthi, Lena Antimicrob Agents Chemother Antiviral Agents Combination antiretroviral therapy (cART) dramatically changed the face of the HIV/AIDS pandemic, making it one of the most prominent medical breakthroughs of the past 3 decades. However, as the life span of persons living with HIV (PLWH) continues to approach that of the general population, the same cannot be said regarding their quality of life. PLWH are affected by comorbid conditions such as high blood pressure, diabetes, and neurocognitive impairment at a higher rate and increased severity than their age-matched counterparts. PLWH also have higher levels of inflammation, the drivers of which are not entirely clear. As cART treatment is lifelong, we assessed here the effects of cART, independent of HIV, on primary human monocyte-derived macrophages (MDMs). MDMs were unskewed or skewed to an alternative phenotype and treated with Atripla or Triumeq, two first-line cART treatments. We report that Triumeq skewed alternative MDMs toward an inflammatory nonsenescent phenotype. Both Atripla and Triumeq caused mitochondrial dysfunction, specifically efavirenz and abacavir. Additionally, transcriptome sequencing (RNA-seq) demonstrated that both Atripla and Triumeq caused differential regulation of genes involved in immune regulation and cell cycle and DNA repair. Collectively, our data demonstrate that cART, independent of HIV, alters the MDM phenotype. This suggests that cART may contribute to cell dysregulation in PLWH that subsequently results in increased susceptibility to comorbidities. American Society for Microbiology 2022-03-16 /pmc/articles/PMC9017340/ /pubmed/35293780 http://dx.doi.org/10.1128/aac.01941-21 Text en Copyright © 2022 Wallace et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Antiviral Agents
Wallace, Jennillee
Gonzalez, Hemil
Rajan, Reshma
Narasipura, Srinivas D.
Virdi, Amber K.
Olali, Arnold Z.
Naqib, Ankur
Arbieva, Zarema
Maienschein-Cline, Mark
Al-Harthi, Lena
Anti-HIV Drugs Cause Mitochondrial Dysfunction in Monocyte-Derived Macrophages
title Anti-HIV Drugs Cause Mitochondrial Dysfunction in Monocyte-Derived Macrophages
title_full Anti-HIV Drugs Cause Mitochondrial Dysfunction in Monocyte-Derived Macrophages
title_fullStr Anti-HIV Drugs Cause Mitochondrial Dysfunction in Monocyte-Derived Macrophages
title_full_unstemmed Anti-HIV Drugs Cause Mitochondrial Dysfunction in Monocyte-Derived Macrophages
title_short Anti-HIV Drugs Cause Mitochondrial Dysfunction in Monocyte-Derived Macrophages
title_sort anti-hiv drugs cause mitochondrial dysfunction in monocyte-derived macrophages
topic Antiviral Agents
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9017340/
https://www.ncbi.nlm.nih.gov/pubmed/35293780
http://dx.doi.org/10.1128/aac.01941-21
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