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Höhne, K. ; Businger, R.* ; van Nuffel, A.* ; Bolduan, S. ; Koppensteiner, H. ; Baeyens, A.* ; Vermeire, J.* ; Malatinkova, E.* ; Verhasselt, B.* ; Schindler, M.

Virion encapsidated HIV-1 Vpr induces NFAT to prime non-activated T cells for productive infection.

Open Biol. 6:160046 (2016)
Verlagsversion Anhang DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The majority of T cells encountered by HIV-1 are non-activated and do not readily allow productive infection. HIV-1 Vpr is highly abundant in progeny virions, and induces signalling and HIV-1 LTR transcription. We hence hypothesized that Vpr might be a determinant of non-activated T-cell infection. Virion-delivered Vpr activated nuclear factor of activated T cells (NFAT) through Ca(2+) influx and interference with the NFAT export kinase GSK3β. This leads to NFAT translocation and accumulation within the nucleus and was required for productive infection of unstimulated primary CD4(+) T cells. A mutagenesis approach revealed correlation of Vpr-mediated NFAT activation with its ability to enhance LTR transcription and mediate cell cycle arrest. Upon NFAT inhibition, Vpr did not augment resting T-cell infection, and showed reduced G2/M arrest and LTR transactivation. Altogether, Vpr renders unstimulated T cells more permissive for productive HIV-1 infection and stimulates activation of productively infected as well as virus-exposed T cells. Therefore, it could be involved in the establishment and reactivation of HIV-1 from viral reservoirs and might have an impact on the levels of immune activation, which are determinants of HIV-1 pathogenesis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Hiv-1 ; Nfat ; Vpr ; Productive T-cell Infection; Immunodeficiency-virus Type-1; Human Lymphoid-tissue; Ex-vivo; Transcription Factor; Gene-expression; Nuclear-factor; Kappa-b; Macrophage Infection; Accessory Proteins; Immune Activation
e-ISSN 2046-2441
Zeitschrift Open Biology
Quellenangaben Band: 6, Heft: 7, Seiten: , Artikelnummer: 160046 Supplement: ,
Verlag Royal Society of London
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)