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

Abstract 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 targ...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Daniel Ivanusic, Kazimierz Madela, Norbert Bannert, Joachim Denner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cf4f484a765a4ecbb333522ff6eab171
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:cf4f484a765a4ecbb333522ff6eab171
record_format	dspace
spelling	oai:doaj.org-article:cf4f484a765a4ecbb333522ff6eab1712021-12-02T17:01:49ZThe large extracellular loop of CD63 interacts with gp41 of HIV-1 and is essential for establishing the virological synapse10.1038/s41598-021-89523-72045-2322https://doaj.org/article/cf4f484a765a4ecbb333522ff6eab1712021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89523-7https://doaj.org/toc/2045-2322Abstract 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.Daniel IvanusicKazimierz MadelaNorbert BannertJoachim DennerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniel Ivanusic Kazimierz Madela Norbert Bannert Joachim Denner The large extracellular loop of CD63 interacts with gp41 of HIV-1 and is essential for establishing the virological synapse
description	Abstract 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.
format	article
author	Daniel Ivanusic Kazimierz Madela Norbert Bannert Joachim Denner
author_facet	Daniel Ivanusic Kazimierz Madela Norbert Bannert Joachim Denner
author_sort	Daniel Ivanusic
title	The large extracellular loop of CD63 interacts with gp41 of HIV-1 and is essential for establishing the virological synapse
title_short	The large extracellular loop of CD63 interacts with gp41 of HIV-1 and is essential for establishing the virological synapse
title_full	The large extracellular loop of CD63 interacts with gp41 of HIV-1 and is essential for establishing the virological synapse
title_fullStr	The large extracellular loop of CD63 interacts with gp41 of HIV-1 and is essential for establishing the virological synapse
title_full_unstemmed	The large extracellular loop of CD63 interacts with gp41 of HIV-1 and is essential for establishing the virological synapse
title_sort	large extracellular loop of cd63 interacts with gp41 of hiv-1 and is essential for establishing the virological synapse
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cf4f484a765a4ecbb333522ff6eab171
work_keys_str_mv	AT danielivanusic thelargeextracellularloopofcd63interactswithgp41ofhiv1andisessentialforestablishingthevirologicalsynapse AT kazimierzmadela thelargeextracellularloopofcd63interactswithgp41ofhiv1andisessentialforestablishingthevirologicalsynapse AT norbertbannert thelargeextracellularloopofcd63interactswithgp41ofhiv1andisessentialforestablishingthevirologicalsynapse AT joachimdenner thelargeextracellularloopofcd63interactswithgp41ofhiv1andisessentialforestablishingthevirologicalsynapse AT danielivanusic largeextracellularloopofcd63interactswithgp41ofhiv1andisessentialforestablishingthevirologicalsynapse AT kazimierzmadela largeextracellularloopofcd63interactswithgp41ofhiv1andisessentialforestablishingthevirologicalsynapse AT norbertbannert largeextracellularloopofcd63interactswithgp41ofhiv1andisessentialforestablishingthevirologicalsynapse AT joachimdenner largeextracellularloopofcd63interactswithgp41ofhiv1andisessentialforestablishingthevirologicalsynapse
_version_	1718382052162666496

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

Ejemplares similares