HIV Replication Increases the Mitochondrial DNA Content of Plasma Extracellular Vesicles
Extracellular vesicles (EVs) and their cargo have been studied intensively as potential sources of biomarkers in HIV infection; however, their DNA content, particularly the mitochondrial portion (mtDNA), remains largely unexplored. It is well known that human immunodeficiency virus (HIV) infection a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/1924 |
| _version_ | 1797624466711248896 |
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| author | Wilfried Wenceslas Bazié Julien Boucher Benjamin Goyer Dramane Kania Isidore Tiandiogo Traoré Diane Yirgnur Somé Michel Alary Caroline Gilbert |
| author_facet | Wilfried Wenceslas Bazié Julien Boucher Benjamin Goyer Dramane Kania Isidore Tiandiogo Traoré Diane Yirgnur Somé Michel Alary Caroline Gilbert |
| author_sort | Wilfried Wenceslas Bazié |
| collection | DOAJ |
| description | Extracellular vesicles (EVs) and their cargo have been studied intensively as potential sources of biomarkers in HIV infection; however, their DNA content, particularly the mitochondrial portion (mtDNA), remains largely unexplored. It is well known that human immunodeficiency virus (HIV) infection and prolonged antiretroviral therapy (ART) lead to mitochondrial dysfunction and reduced mtDNA copy in cells and tissues. Moreover, mtDNA is a well-known damage-associated molecular pattern molecule that could potentially contribute to increased immune activation, oxidative stress, and inflammatory response. We investigated the mtDNA content of large and small plasma EVs in persons living with HIV (PLWH) and its implications for viral replication, ART use, and immune status. Venous blood was collected from 196 PLWH, ART-treated or ART-naïve (66 with ongoing viral replication, ≥20 copies/mL), and from 53 HIV-negative persons, all recruited at five HIV testing or treatment centers in Burkina Faso. Large and small plasma EVs were purified and counted, and mtDNA level was measured by RT-qPCR. Regardless of HIV status, mtDNA was more abundant in large than small EVs. It was more abundant in EVs of viremic than aviremic and control participants and tended to be more abundant in participants treated with Tenofovir compared with Zidovudine. When ART treatment was longer than six months and viremia was undetectable, no variation in EV mtDNA content versus CD4 and CD8 count or CD4/CD8 ratio was observed. However, mtDNA in large and small EVs decreased with years of HIV infection and ART. Our results highlight the impact of viral replication and ART on large and small EVs’ mtDNA content. The mechanisms underlying the differential incorporation of mtDNA into EVs and their effects on the surrounding cells warrant further investigation. |
| first_indexed | 2024-03-11T09:42:44Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:42:44Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-50f913638f36403083f56322f94c9c8d2023-11-16T16:49:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243192410.3390/ijms24031924HIV Replication Increases the Mitochondrial DNA Content of Plasma Extracellular VesiclesWilfried Wenceslas Bazié0Julien Boucher1Benjamin Goyer2Dramane Kania3Isidore Tiandiogo Traoré4Diane Yirgnur Somé5Michel Alary6Caroline Gilbert7Axe de Recherche Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec-Université Laval, Québec, QC G1V 4G2, CanadaAxe de Recherche Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec-Université Laval, Québec, QC G1V 4G2, CanadaAxe de Recherche Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec-Université Laval, Québec, QC G1V 4G2, CanadaProgramme de Recherche sur les Maladies Infectieuses, Centre Muraz, Institut National de Santé Publique, Bobo-Dioulasso 01 BP 390, Burkina FasoProgramme de Recherche sur les Maladies Infectieuses, Centre Muraz, Institut National de Santé Publique, Bobo-Dioulasso 01 BP 390, Burkina FasoProgramme de Recherche sur les Maladies Infectieuses, Centre Muraz, Institut National de Santé Publique, Bobo-Dioulasso 01 BP 390, Burkina FasoAxe de Recherche Santé des Populations et Pratiques Optimales en Santé, Centre de Recherche du CHU de Québec-Université Laval, Québec, QC G1S 4L8, CanadaAxe de Recherche Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec-Université Laval, Québec, QC G1V 4G2, CanadaExtracellular vesicles (EVs) and their cargo have been studied intensively as potential sources of biomarkers in HIV infection; however, their DNA content, particularly the mitochondrial portion (mtDNA), remains largely unexplored. It is well known that human immunodeficiency virus (HIV) infection and prolonged antiretroviral therapy (ART) lead to mitochondrial dysfunction and reduced mtDNA copy in cells and tissues. Moreover, mtDNA is a well-known damage-associated molecular pattern molecule that could potentially contribute to increased immune activation, oxidative stress, and inflammatory response. We investigated the mtDNA content of large and small plasma EVs in persons living with HIV (PLWH) and its implications for viral replication, ART use, and immune status. Venous blood was collected from 196 PLWH, ART-treated or ART-naïve (66 with ongoing viral replication, ≥20 copies/mL), and from 53 HIV-negative persons, all recruited at five HIV testing or treatment centers in Burkina Faso. Large and small plasma EVs were purified and counted, and mtDNA level was measured by RT-qPCR. Regardless of HIV status, mtDNA was more abundant in large than small EVs. It was more abundant in EVs of viremic than aviremic and control participants and tended to be more abundant in participants treated with Tenofovir compared with Zidovudine. When ART treatment was longer than six months and viremia was undetectable, no variation in EV mtDNA content versus CD4 and CD8 count or CD4/CD8 ratio was observed. However, mtDNA in large and small EVs decreased with years of HIV infection and ART. Our results highlight the impact of viral replication and ART on large and small EVs’ mtDNA content. The mechanisms underlying the differential incorporation of mtDNA into EVs and their effects on the surrounding cells warrant further investigation.https://www.mdpi.com/1422-0067/24/3/1924extracellular vesiclesHIV-1mitochondrial DNAantiretroviral therapytenofovirzidovudine |
| spellingShingle | Wilfried Wenceslas Bazié Julien Boucher Benjamin Goyer Dramane Kania Isidore Tiandiogo Traoré Diane Yirgnur Somé Michel Alary Caroline Gilbert HIV Replication Increases the Mitochondrial DNA Content of Plasma Extracellular Vesicles International Journal of Molecular Sciences extracellular vesicles HIV-1 mitochondrial DNA antiretroviral therapy tenofovir zidovudine |
| title | HIV Replication Increases the Mitochondrial DNA Content of Plasma Extracellular Vesicles |
| title_full | HIV Replication Increases the Mitochondrial DNA Content of Plasma Extracellular Vesicles |
| title_fullStr | HIV Replication Increases the Mitochondrial DNA Content of Plasma Extracellular Vesicles |
| title_full_unstemmed | HIV Replication Increases the Mitochondrial DNA Content of Plasma Extracellular Vesicles |
| title_short | HIV Replication Increases the Mitochondrial DNA Content of Plasma Extracellular Vesicles |
| title_sort | hiv replication increases the mitochondrial dna content of plasma extracellular vesicles |
| topic | extracellular vesicles HIV-1 mitochondrial DNA antiretroviral therapy tenofovir zidovudine |
| url | https://www.mdpi.com/1422-0067/24/3/1924 |
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