Cover Image

HIV-Nef and ADAM17-containing plasma extracellular vesicles induce and correlate with immune pathogenesis in chronic HIV infection

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 inf...

Full description

Saved in:
Bibliographic Details
Main Authors: Lee, Jung-Hyun (Author) , Schierer, Stephan (Author) , Blume, Katja (Author) , Dindorf, Jochen (Author) , Wittki, Sebastian (Author) , Xiang, Wei (Author) , Ostalecki, Christian (Author) , Koliha, Nina (Author) , Wild, Stefan (Author) , Schuler, Gerold (Author) , Fackler, Oliver Till (Author) , Saksela, Kalle (Author) , Harrer, Thomas (Author) , Baur, Andreas S. (Author)
Format: Article (Journal)
Language:English
Published: 3 March 2016
In: EBioMedicine
Year: 2016, Volume: 6, Pages: 103-113
ISSN:2352-3964
DOI:10.1016/j.ebiom.2016.03.004
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ebiom.2016.03.004
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S2352396416300871
Get full text
Author Notes:Jung-Hyun Lee, Stephan Schierer, Katja Blume, Jochen Dindorf, Sebastian Wittki, Wei Xiang, Christian Ostalecki, Nina Koliha, Stefan Wild, Gerold Schuler, Oliver T. Fackler, Kalle Saksela, Thomas Harrer, Andreas S. Baur
Description
Summary: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 αvβ3 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.
Item Description:Gesehen am 17.06.2020
Physical Description:Online Resource
ISSN:2352-3964
DOI:10.1016/j.ebiom.2016.03.004

Similar Items