HIV Replication Increases the Mitochondrial DNA Content of Plasma Extracellular Vesicles
Abstract
:1. Introduction
2. Results
2.1. Mitochondrial DNA Is More Abundant in EVs of ART-Naive Viremic Patients
2.2. ART including Tenofovir Increases the mtDNA Content of EVs
2.3. EV-Borne mtDNA Abundance Appears Indifferent to CD4 and CD8 T Cell Counts
2.4. Men Who Have Sex with Men Have More Small-EV-Borne mtDNA
2.5. The mtDNA Content of Large EVs Can Distinguish HIV+ Viremic Patients
3. Discussion
4. Materials and Methods
4.1. Study Participants
4.2. Quantitation of HIV-1 RNA, CD4 and CD8 T Lymphocytes
4.3. Purification of Extracellular Vesicles
4.4. EV Size Measurement
4.5. EV Flow Cytometry Analysis
4.6. Detergent Treatment of Extracellular Vesicles
4.7. DNA Extraction and Mitochondrial DNA Quantification
4.8. Transmission Electron Microscopy
4.9. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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HIV–Control (Never Infected) n = 53 | HIV+ n = 196 | p Value | HIV+ ART > 6 Months, VL Undetectable n = 118 | HIV+ ART-Naïve, VL Undetectable n = 12 | p Value | HIV+ ART > 6 Months, VL Detectable n = 51 | HIV+ ART-Naïve, VL Detectable n = 15 | p Value | |
---|---|---|---|---|---|---|---|---|---|
Male: n (%) | 14 (26.4) | 54 (27.5) | 0.8692 | 29 (24.6) | 5 (41.67) | 0.1993 | 14 (27.45) | 6 (40.00) | 0.3525 |
Female sex workers: n (%) | - | 85 (43.4) | - | 58 (49.1) | 1 (8.3) | 0.0002 | 24 (47.1) | 2 (13.3) | 0.0870 |
Men who have sex with men: n (%) | - | 33 (16.8) | - | 20 (16.9) | 0 (0.0) | 9 (17.6) | 4 (26.7) | ||
Age in years, median (IQR) | 25 (22–32) | 37 (31–44) | <0.0001 | 38 (32–44) | 43 (28–52) | 0.2072 | 35 (30–42) | 35 (26–42) | 0.4629 |
HIV+ duration, median months (IQR) | - | 43 (22–121) | - | 50 (24–120) | 24 (12–72) | 0.1229 | 43 (24–117) | 8 (1–114) | 0.4643 |
CD4 T cells/µL, median (IQR) | 937 (800–1316) | 473 (340–696) | <0.0001 | 492 (368–750) | 717 (466–875) | 0.1057 | 372 (188–507) | 632 (304–798) | 0.0691 |
CD8 T cells/µL, median (IQR) | 564 (451–717) | 757 (535–1011) | <0.0001 | 739 (536–1089) | 650 (398–759) | 0.1245 | 856 (544–1016) | 791 (556–1016) | 0.4482 |
CD4/CD8 ratio, median (IQR) | 1.8 (1.4–2.1) | 0.6 (0.4–1.0) | <0.0001 | 0.7 (0.5–1.0) | 1.2 (0.7–1.5) | 0.0028 | 0.4 (0.2–0.7) | 0.7 (0.5–1.2) | 0.0120 |
ART, n (%) | - | 169 (86.22) | 118 (100) | 0 | 51 (100) | 0 | |||
NRTI ART drugs, n (%) | - | ||||||||
Abacavir | - | 7 (4.1) | 3 (2.5) | - | 4 (7.8) | - | |||
Tenofovir | - | 112 (66.3) | 80 (67.8) | - | 32 (62.7) | - | |||
Zidovudine | - | 50 (29.6) | 35 (29.7) | - | 15 (29.4) | - | |||
NNRTI ART drugs or PI, n (%) | - | ||||||||
Efavirenz | - | 104 (61.5) | 73 (61.9) | - | 31 (60.8) | - | |||
Nevirapine | - | 46 (27.2) | 35 (29.7) | - | 11 (21.6) | - | |||
Protease inhibitors | - | 19 (11.2) | 10 (8.5) | - | 9 (17.6) | - | |||
Months on ART, median (IQR) | - | 36 (21–88) | 38 (21–92) | - | 24 (21–69) | - | |||
HIV undetectable (<20 copies/mL) while on ART, n (%) | - | 118 (69.8) | - | - | - | - | |||
HIV load, median copies/mL (IQR) | - | 2.841 (82–29.240) | - | - | 1.606 (77–22.510) | 13.174 (2.297–70.711) | 0.2451 |
Female Sex Workers (n = 58) | Men Who Have Sex with Men (n = 20) | Females from General Population (n = 31) | Males from General Population (n = 9) | p Value | |
---|---|---|---|---|---|
Age, median (IQR) | 38 (33–44) | 30 (25–38) | 42 (35–46) | 45 (45–46) | 0.0003 |
CD4 T cell count, median (IQR) | 507 (372–825) | 485 (351–565) | 543 (434–758) | 295 (265–455) | 0.0759 |
CD8 T cell count, median (IQR) | 748 (569–1075) | 559 (430–653) | 822 (590–1206) | 751 (540–856) | 0.1768 |
Years HIV+, median (IQR) | 6.0 (3.1–10.0) | 1.7 (1.0–4.0) | 7.1 (2.0–12.8) | 2.0 (1.5–7.0) | 0.0108 |
Years on ART, median (IQR) | 4.6 (2.6–8) | 1.7 (1.1–2.2) | 5.3 (2.0–10.0) | 1.0 (0.9–6.6) | 0.0021 |
On Tenofovir, n (%) | 33 (56.9) | 20 (100) | 20 (64.5) | 7 (77.8) | 0.0012 |
Large EV count, log10 EVs/µL plasma, median (IQR) | 3.6 (3.4–3.8) | 3.7 (3.6–3.8) | 3.7 (3.4–4.1) | 4.2 (4.0–4.3) | 0.0006 |
Small EV count, log10 EVs/µL plasma, median (IQR) | 4.0 (3.9–4.4) | 4.0 (3.8–4.1) | 3.9 (3.8–4.4) | 4.3 (3.8–4.4) | 0.1540 |
Female Sex Workers (n = 26) | Men Who Have Sex with Men (n = 13) | Females from General Population (n = 20) | Males from General Population (n = 7) | p Value | |
---|---|---|---|---|---|
Age, median (IQR) | 35 (33–41) | 25 (25–29) | 40 (33–44) | 35 (25–49) | <0.0001 |
CD4 T cell count, median (IQR) | 394 (266–550) | 395 (321–514) | 465 (176–703) | 208 (164–563) | 0.4819 |
CD8 T cell count, median (IQR) | 883 (641–1013) | 770 (438–913) | 729 (543–1196) | 630 (480–1147) | 0.2414 |
Viral copies/mL, median (IQR) | 2432 (90–38,126) | 5442 (98–19,481) | 3632 (72–34,053) | 1563 (186–35,481) | 0.6147 |
Years HIV+, median (IQR) | 3.7 (2.0–10.8) | 0.8 (0.5–2.1) | 6.0 (3.3–13.0) | 1.7 (0.8–18.8) | 0.0053 |
ART-treated, n (%) | 24 (92.3) | 9 (69.2) | 13 (65.0) | 5 (71.4) | 0.0869 |
Years on ART, median (IQR) | 3.4 (2.0–7.2) | 1.0 (0.7–2.0) | 5.0 (2.4–7.5) | 0.7 (0.7–6.1) | 0.0385 |
On Tenofovir, n (%) | 12 (50) | 9 (100) | 8 (61) | 3 (60) | 0.0908 |
Large EV count, log10 EVs/µL plasma, median (IQR) | 3.8 (3.6–4.0) | 3.9 (3.8–4.1) | 4.1 (3.5–4.2) | 4.3 (4.1–4.5) | 0.0375 |
Small EV count, log10 EVs/µL plasma, median (IQR) | 3.9 (3.8–4.4) | 3.9 (3.8–4.0) | 3.9 (3.8–4.5) | 4.2 (3.8–4.5) | 0.6392 |
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Bazié, W.W.; Boucher, J.; Goyer, B.; Kania, D.; Traoré, I.T.; Somé, D.Y.; Alary, M.; Gilbert, C. HIV Replication Increases the Mitochondrial DNA Content of Plasma Extracellular Vesicles. Int. J. Mol. Sci. 2023, 24, 1924. https://doi.org/10.3390/ijms24031924
Bazié WW, Boucher J, Goyer B, Kania D, Traoré IT, Somé DY, Alary M, Gilbert C. HIV Replication Increases the Mitochondrial DNA Content of Plasma Extracellular Vesicles. International Journal of Molecular Sciences. 2023; 24(3):1924. https://doi.org/10.3390/ijms24031924
Chicago/Turabian StyleBazié, Wilfried Wenceslas, Julien Boucher, Benjamin Goyer, Dramane Kania, Isidore Tiandiogo Traoré, Diane Yirgnur Somé, Michel Alary, and Caroline Gilbert. 2023. "HIV Replication Increases the Mitochondrial DNA Content of Plasma Extracellular Vesicles" International Journal of Molecular Sciences 24, no. 3: 1924. https://doi.org/10.3390/ijms24031924