Massive Release of CD9+ Microvesicles in Human Immunodeficiency Virus Infection, Regardless of Virologic Control

• Published in: The Journal of infectious diseases Vol. 225; no. 6; pp. 1040 - 1049
• Main Authors: Poveda, Eva, Tabernilla, Andrés, Fitzgerald, Wendy, Salgado-Barreira, Ángel, Grandal, Marta, Pérez, Alexandre, Mariño, Ana, Álvarez, Hortensia, Valcarce, Nieves, González-García, Juan, Bernardino, José Ignacio, Gutierrez, Félix, Fujioka, Hisashi, Crespo, Manuel, Ruiz-Mateos, Ezequiel, Margolis, Leonid, Lederman, Michael M, Freeman, Michael L
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 15.03.2022
• Subjects: Antiretroviral drugs; Antiretroviral therapy; CD9 antigen; Cell-Derived Microparticles; DNA, Mitochondrial; Extracellular Vesicles; Flow cytometry; HIV; HIV Infections; Human immunodeficiency virus; Humans; Immune system; Infections; Major and Brief Reports; Mitochondria; Mitochondrial DNA; Pathogenesis; Platelets; Polymerase chain reaction; Tetraspanin 29; Viremia; elite controllers; extracellular vesicles; microvesicles; HIV; mitochondria
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiaa375

Abstract Background The role of extracellular vesicles (EVs) in human immunodeficiency virus (HIV) pathogenesis is unknown. We examine the cellular origin of plasma microvesicles (MVs), a type of ectocytosis-derived EV, the presence of mitochondria in MVs, and their relationship to circulating cell-free mitochondrial deoxyribonucleic acid (ccf-mtDNA) in HIV-infected patients and controls. Methods Five participant groups were defined: 30 antiretroviral therapy (ART)-naive; 30 ART-treated with nondetectable viremia; 30 elite controllers; 30 viremic controllers; and 30 HIV-uninfected controls. Microvesicles were quantified and characterized from plasma samples by flow cytometry. MitoTrackerDeepRed identified MVs containing mitochondria and ccf-mtDNA was quantified by real-time polymerase chain reaction. Results Microvesicle numbers were expanded at least 10-fold in all HIV-infected groups compared with controls. More than 79% were platelet-derived MVs. Proportions of MVs containing mitochondria (22.3% vs 41.6%) and MV mitochondrial density (706 vs 1346) were significantly lower among HIV-infected subjects than controls, lowest levels for those on ART. Microvesicle numbers correlated with ccf-mtDNA levels that were higher among HIV-infected patients. Conclusions A massive release of platelet-derived MVs occurs during HIV infection. Some MVs contain mitochondria, but their proportion and mitochondrial densities were lower in HIV infection than in controls. Platelet-derived MVs may be biomarkers of platelet activation, possibly reflecting pathogenesis even in absence of HIV replication. A massive release of platelet-derived CD9+ microvesicles occurs during HIV infection, regardless of virologic control or antiretroviral therapy administration. Some of these microvesicles contain mitochondria, but their prevalence and mitochondrial density are reduced in HIV infection.