The KGD Motif of Epstein-Barr Virus gH/gL Is Bifunctional, Orchestrating Infection of B Cells and Epithelial Cells

ABSTRACT Epstein-Barr virus (EBV), a member of the herpesvirus family, is the causative agent of common human infections and specific malignancies. EBV entry into target cells, including B cells and epithelial cells, requires the interaction of multiple virus-encoded glycoproteins. Glycoproteins H a...

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Autores principales:	Jia Chen, Cynthia L. Rowe, Theodore S. Jardetzky, Richard Longnecker
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2012
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ca3be0cf8d8741a38f331a9cd7e55e29
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spelling	oai:doaj.org-article:ca3be0cf8d8741a38f331a9cd7e55e292021-11-15T15:39:02ZThe KGD Motif of Epstein-Barr Virus gH/gL Is Bifunctional, Orchestrating Infection of B Cells and Epithelial Cells10.1128/mBio.00290-112150-7511https://doaj.org/article/ca3be0cf8d8741a38f331a9cd7e55e292012-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00290-11https://doaj.org/toc/2150-7511ABSTRACT Epstein-Barr virus (EBV), a member of the herpesvirus family, is the causative agent of common human infections and specific malignancies. EBV entry into target cells, including B cells and epithelial cells, requires the interaction of multiple virus-encoded glycoproteins. Glycoproteins H and L (gH/gL) cooperate with glycoprotein B (gB) to mediate fusion of the viral envelope with target cell membranes. Both the gH/gL complex and gB are required for fusion, whereas glycoprotein 42 (gp42) acts as a tropism switch and is required for B cell infection and inhibits epithelial cell infection. Our previous studies identified a prominent KGD motif located on the surface of gH/gL. In the current study, we found that this motif serves as a bifunctional domain on the surface of gH/gL that directs EBV fusion of B cells and epithelial cells. Mutation of the KGD motif to AAA decreased fusion with both epithelial and B cells and reduced the binding of gH/gL to epithelial cells and to gp42. We also demonstrate that deletion of amino acids 62 to 66 of gp42 selectively reduces binding to wild-type gH/gL, but not the KGD mutant, suggesting that the KGD motif of gH/gL interacts with the N-terminal amino acids 62 to 66 of gp42. IMPORTANCE Epithelial and B cells are the major targets of Epstein-Barr virus (EBV) infection in the human host. EBV utilizes different glycoprotein complexes to enter these cell types. For B cell fusion, EBV uses complexes containing gp42, gH/gL, and gB, whereas just gH/gL and gB are required for epithelial cell fusion. In the current study, a bifunctional domain consisting of a prominent KGD motif on the surface of the gH/gL structure was identified; this domain affects interactions with gp42 or epithelial receptors, ultimately dictating with which cell type virus-induced fusion can occur. These studies will lead to a better understanding of the mechanism of EBV-induced membrane fusion and herpesvirus-induced membrane fusion in general.Jia ChenCynthia L. RoweTheodore S. JardetzkyRichard LongneckerAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 3, Iss 1 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jia Chen Cynthia L. Rowe Theodore S. Jardetzky Richard Longnecker The KGD Motif of Epstein-Barr Virus gH/gL Is Bifunctional, Orchestrating Infection of B Cells and Epithelial Cells
description	ABSTRACT Epstein-Barr virus (EBV), a member of the herpesvirus family, is the causative agent of common human infections and specific malignancies. EBV entry into target cells, including B cells and epithelial cells, requires the interaction of multiple virus-encoded glycoproteins. Glycoproteins H and L (gH/gL) cooperate with glycoprotein B (gB) to mediate fusion of the viral envelope with target cell membranes. Both the gH/gL complex and gB are required for fusion, whereas glycoprotein 42 (gp42) acts as a tropism switch and is required for B cell infection and inhibits epithelial cell infection. Our previous studies identified a prominent KGD motif located on the surface of gH/gL. In the current study, we found that this motif serves as a bifunctional domain on the surface of gH/gL that directs EBV fusion of B cells and epithelial cells. Mutation of the KGD motif to AAA decreased fusion with both epithelial and B cells and reduced the binding of gH/gL to epithelial cells and to gp42. We also demonstrate that deletion of amino acids 62 to 66 of gp42 selectively reduces binding to wild-type gH/gL, but not the KGD mutant, suggesting that the KGD motif of gH/gL interacts with the N-terminal amino acids 62 to 66 of gp42. IMPORTANCE Epithelial and B cells are the major targets of Epstein-Barr virus (EBV) infection in the human host. EBV utilizes different glycoprotein complexes to enter these cell types. For B cell fusion, EBV uses complexes containing gp42, gH/gL, and gB, whereas just gH/gL and gB are required for epithelial cell fusion. In the current study, a bifunctional domain consisting of a prominent KGD motif on the surface of the gH/gL structure was identified; this domain affects interactions with gp42 or epithelial receptors, ultimately dictating with which cell type virus-induced fusion can occur. These studies will lead to a better understanding of the mechanism of EBV-induced membrane fusion and herpesvirus-induced membrane fusion in general.
format	article
author	Jia Chen Cynthia L. Rowe Theodore S. Jardetzky Richard Longnecker
author_facet	Jia Chen Cynthia L. Rowe Theodore S. Jardetzky Richard Longnecker
author_sort	Jia Chen
title	The KGD Motif of Epstein-Barr Virus gH/gL Is Bifunctional, Orchestrating Infection of B Cells and Epithelial Cells
title_short	The KGD Motif of Epstein-Barr Virus gH/gL Is Bifunctional, Orchestrating Infection of B Cells and Epithelial Cells
title_full	The KGD Motif of Epstein-Barr Virus gH/gL Is Bifunctional, Orchestrating Infection of B Cells and Epithelial Cells
title_fullStr	The KGD Motif of Epstein-Barr Virus gH/gL Is Bifunctional, Orchestrating Infection of B Cells and Epithelial Cells
title_full_unstemmed	The KGD Motif of Epstein-Barr Virus gH/gL Is Bifunctional, Orchestrating Infection of B Cells and Epithelial Cells
title_sort	kgd motif of epstein-barr virus gh/gl is bifunctional, orchestrating infection of b cells and epithelial cells
publisher	American Society for Microbiology
publishDate	2012
url	https://doaj.org/article/ca3be0cf8d8741a38f331a9cd7e55e29
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The KGD Motif of Epstein-Barr Virus gH/gL Is Bifunctional, Orchestrating Infection of B Cells and Epithelial Cells

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