Publication Database

The large extracellular loop of CD63 interacts with gp41 of HIV-1 and is essential for establishing the virological synapse (2021)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Ivanusic, Daniel

Madela, Kazimierz

Bannert, Norbert

Denner, Joachim (WE 5)

Quelle

Scientific reports

Bandzählung: 11

Heftzählung: 1

Seiten: Article number: 10011

ISSN: 2045-2322

Sprache

Englisch

Verweise

URL (Volltext): https://www.nature.com/articles/s41598-021-89523-7

DOI: 10.1038/s41598-021-89523-7

Pubmed: 33976357

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Human immunodeficiency virus type 1 (HIV-1) persists lifelong in infected individuals and has evolved unique strategies in order to evade the immune system. One of these strategies is the direct cell-to-cell spread of HIV-1. The formation of a virological synapse (VS) between donor and target cell is important for this process. Tetraspanins are cellular proteins that are actively involved in the formation of a VS. However, the molecular mechanisms of recruiting host proteins for the cell-cell transfer of particles to the VS remains unclear. Our study has mapped the binding site for the transmembrane envelope protein gp41 of HIV-1 within the large extracellular loop (LEL) of CD63 and showed that this interaction occurs predominantly at the VS between T cells where viral particles are transferred. Mutations within the highly conserved CCG motif of the tetraspanin superfamily abrogated recruiting of expressed HIV-1 GFP fused Gag core protein and CD63 to the VS. This demonstrates the biological significance of CD63 for enhanced formation of a VS. Since cell-cell spread of HIV-1 is a major route of persistent infection, these results highlight the central role of CD63 as a member of the tetraspanin superfamily during HIV-1 infection and pathogenesis.