HIV-Nef and ADAM17-Containing Plasma Extracellular Vesicles Induce and Correlate with Immune Pathogenesis in Chronic HIV Infection

Journal article


Publication Details

Author(s): Lee JH, Schierer S, Blume K, Dindorf J, Wittki S, Xiang W, Ostalecki C, Koliha N, Wild S, Schuler G, Fackler OT, Saksela K, Harrer T, Baur A
Journal: EBioMedicine
Publication year: 2016
Volume: 6
Pages range: 103-13
ISSN: 2352-3964


Abstract


Antiretroviral therapy (ART) efficiently suppresses HIV replication but immune activation and low CD4 T cell counts often persist. The underlying mechanism of this ART-resistant pathogenesis is not clear. We observed that levels of plasma extracellular vesicles (pEV) are strongly elevated in HIV infection and do not decline during ART. Surprisingly, these vesicles contained the viral accessory proteins Nef and Vpu, which are assumed to be not expressed under efficient ART, as well as pro-inflammatory effectors, including activated ADAM17. HIV pEV were characterized by the presence of activated ?v?3 and absence of CD81 and Tsg101. Correlating with immune activation, peripheral monocytes ingested large amounts of pEV, giving rise to an increased population of CD1c(+) CD14(+) cells that secreted inflammatory cytokines. Importantly, the pro-inflammatory content, particularly ADAM17 activity, correlated with low T cell counts. Preliminary evidence suggested that HIV pEV derived from peripheral mononuclear cells and from an unknown myeloid cell population. In summary we propose an important role of pro-inflammatory pEV in chronic HIV infection due to ongoing viral Nef activity.



FAU Authors / FAU Editors

Harrer, Thomas Prof. Dr.
Professur für Innere Medizin mit dem Schwerpunkt Immundefizienz
Schuler, Gerold Prof. Dr.
Lehrstuhl für Haut- und Geschlechtskrankheiten
Xiang, Wei PD Dr.
Lehrstuhl für Biochemie und Molekulare Medizin


External institutions
Helsingin yliopisto / University of Helsinki
Miltenyi Biotec GmbH
Universitätsklinikum Heidelberg


How to cite

APA:
Lee, J.-H., Schierer, S., Blume, K., Dindorf, J., Wittki, S., Xiang, W.,... Baur, A. (2016). HIV-Nef and ADAM17-Containing Plasma Extracellular Vesicles Induce and Correlate with Immune Pathogenesis in Chronic HIV Infection. EBioMedicine, 6, 103-13. https://dx.doi.org/10.1016/j.ebiom.2016.03.004

MLA:
Lee, Jung-Hyun, et al. "HIV-Nef and ADAM17-Containing Plasma Extracellular Vesicles Induce and Correlate with Immune Pathogenesis in Chronic HIV Infection." EBioMedicine 6 (2016): 103-13.

BibTeX: 

Last updated on 2018-07-10 at 02:44