Human herpesvirus 8 molecular mimicry of ephrin ligands facilitates cell entry and triggers EphA2 signaling.

Human herpesvirus 8 (HHV-8) is an oncogenic virus that enters cells by fusion of the viral and endosomal cellular membranes in a process mediated by viral surface glycoproteins. One of the cellular receptors hijacked by HHV-8 to gain access to cells is the EphA2 tyrosine kinase receptor, and the mec...

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Autores principales:	Taylor P Light, Delphine Brun, Pablo Guardado-Calvo, Riccardo Pederzoli, Ahmed Haouz, Frank Neipel, Félix A Rey, Kalina Hristova, Marija Backovic
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a2c619e3194f40bca4563a251b741f12
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spelling	oai:doaj.org-article:a2c619e3194f40bca4563a251b741f122021-12-02T19:54:36ZHuman herpesvirus 8 molecular mimicry of ephrin ligands facilitates cell entry and triggers EphA2 signaling.1544-91731545-788510.1371/journal.pbio.3001392https://doaj.org/article/a2c619e3194f40bca4563a251b741f122021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3001392https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Human herpesvirus 8 (HHV-8) is an oncogenic virus that enters cells by fusion of the viral and endosomal cellular membranes in a process mediated by viral surface glycoproteins. One of the cellular receptors hijacked by HHV-8 to gain access to cells is the EphA2 tyrosine kinase receptor, and the mechanistic basis of EphA2-mediated viral entry remains unclear. Using X-ray structure analysis, targeted mutagenesis, and binding studies, we here show that the HHV-8 envelope glycoprotein complex H and L (gH/gL) binds with subnanomolar affinity to EphA2 via molecular mimicry of the receptor's cellular ligands, ephrins (Eph family receptor interacting proteins), revealing a pivotal role for the conserved gH residue E52 and the amino-terminal peptide of gL. Using FSI-FRET and cell contraction assays, we further demonstrate that the gH/gL complex also functionally mimics ephrin ligand by inducing EphA2 receptor association via its dimerization interface, thus triggering receptor signaling for cytoskeleton remodeling. These results now provide novel insight into the entry mechanism of HHV-8, opening avenues for the search of therapeutic agents that could interfere with HHV-8-related diseases.Taylor P LightDelphine BrunPablo Guardado-CalvoRiccardo PederzoliAhmed HaouzFrank NeipelFélix A ReyKalina HristovaMarija BackovicPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 19, Iss 9, p e3001392 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Taylor P Light Delphine Brun Pablo Guardado-Calvo Riccardo Pederzoli Ahmed Haouz Frank Neipel Félix A Rey Kalina Hristova Marija Backovic Human herpesvirus 8 molecular mimicry of ephrin ligands facilitates cell entry and triggers EphA2 signaling.
description	Human herpesvirus 8 (HHV-8) is an oncogenic virus that enters cells by fusion of the viral and endosomal cellular membranes in a process mediated by viral surface glycoproteins. One of the cellular receptors hijacked by HHV-8 to gain access to cells is the EphA2 tyrosine kinase receptor, and the mechanistic basis of EphA2-mediated viral entry remains unclear. Using X-ray structure analysis, targeted mutagenesis, and binding studies, we here show that the HHV-8 envelope glycoprotein complex H and L (gH/gL) binds with subnanomolar affinity to EphA2 via molecular mimicry of the receptor's cellular ligands, ephrins (Eph family receptor interacting proteins), revealing a pivotal role for the conserved gH residue E52 and the amino-terminal peptide of gL. Using FSI-FRET and cell contraction assays, we further demonstrate that the gH/gL complex also functionally mimics ephrin ligand by inducing EphA2 receptor association via its dimerization interface, thus triggering receptor signaling for cytoskeleton remodeling. These results now provide novel insight into the entry mechanism of HHV-8, opening avenues for the search of therapeutic agents that could interfere with HHV-8-related diseases.
format	article
author	Taylor P Light Delphine Brun Pablo Guardado-Calvo Riccardo Pederzoli Ahmed Haouz Frank Neipel Félix A Rey Kalina Hristova Marija Backovic
author_facet	Taylor P Light Delphine Brun Pablo Guardado-Calvo Riccardo Pederzoli Ahmed Haouz Frank Neipel Félix A Rey Kalina Hristova Marija Backovic
author_sort	Taylor P Light
title	Human herpesvirus 8 molecular mimicry of ephrin ligands facilitates cell entry and triggers EphA2 signaling.
title_short	Human herpesvirus 8 molecular mimicry of ephrin ligands facilitates cell entry and triggers EphA2 signaling.
title_full	Human herpesvirus 8 molecular mimicry of ephrin ligands facilitates cell entry and triggers EphA2 signaling.
title_fullStr	Human herpesvirus 8 molecular mimicry of ephrin ligands facilitates cell entry and triggers EphA2 signaling.
title_full_unstemmed	Human herpesvirus 8 molecular mimicry of ephrin ligands facilitates cell entry and triggers EphA2 signaling.
title_sort	human herpesvirus 8 molecular mimicry of ephrin ligands facilitates cell entry and triggers epha2 signaling.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/a2c619e3194f40bca4563a251b741f12
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Human herpesvirus 8 molecular mimicry of ephrin ligands facilitates cell entry and triggers EphA2 signaling.

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