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Lambelé, M.* ; Koppensteiner, H. ; Symeonides, M.* ; Roy, N.H.* ; Chan, J.* ; Schindler, M. ; Thali, M.*

Vpu is the main determinant for tetraspanin downregulation in HIV-1 infected cells.

J. Virol. 89, 3247-3255 (2015)
Verlagsversion DOI PMC
Closed
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Tetraspanins constitute a family of cellular proteins that organize various membrane-based processes. Several members of this family, including CD81, are actively recruited by HIV-1 Gag to viral assembly and release sites. Despite their enrichment at viral exit sites, the overall levels of tetraspanins are decreased in HIV-1-infected cells. Here, we identify Vpu as the main viral determinant for tetraspanin downregulation. We also show that reduction of CD81 levels by Vpu is not a by-product of CD4 or BST-2/Tetherin elimination from the surface of infected cells and likely occurs through an interaction between Vpu and CD81. Finally, we document that Vpu-mediated downregulation of CD81 from the surface of infected T cells can contribute to preserving the infectiousness of viral particles, thus revealing a novel Vpu function that promotes virus propagation by modulating the host cell environment. IMPORTANCE: The HIV-1 accessory protein Vpu has previously been shown to downregulate various host-cell factors, thus helping the virus to overcome restriction barriers, evade immune attack, and maintain the infectivity of viral particles. Our study identifies tetraspanins as an additional group of host factors whose expression at the surface of infected cells is lowered by Vpu. While the downregulation of these integral membrane proteins, including CD81 and CD82, likely affects more than one function of HIV-1-infected cells, we document that Vpu-mediated lowering of CD81 levels in viral particles can be critical to maintaining their infectiousness.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Immunodeficiency-virus Type-1; Hiv-1 Virological Synapse; T-cells; Membrane-proteins; Plasma-membrane; Enriched Microdomains; Accessory Proteins; Surface Receptors; Nef; Infection
Sprache englisch
Veröffentlichungsjahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 0022-538X
e-ISSN 1098-5514
Zeitschrift Journal of Virology
Quellenangaben Band: 89, Heft: 6, Seiten: 3247-3255 Artikelnummer: , Supplement: ,
Verlag American Society for Microbiology (ASM)
Verlagsort Washington
Begutachtungsstatus Peer reviewed
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-502700-006
PubMed ID 25568205
Scopus ID 84923165631
Erfassungsdatum 2015-01-10