Ephrin Receptor A4 is a New Kaposi's Sarcoma-Associated Herpesvirus Virus Entry Receptor.

MBio
Jia ChenRichard Longnecker

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with the development of Kaposi's sarcoma (KS). KSHV target cells include endothelial cells, B cells, monocytes, epithelial cells, dendritic cells, macrophages, and fibroblasts. KSHV entry into target cells is a complex multistep process and is initiated by the binding and interaction of viral envelope glycoproteins with the cellular receptors. In the current studies, we have found that EphA4 promotes KSHV glycoprotein H/glycoprotein L (gH/gL)-mediated fusion and infection better than does ephrin A2 (EphA2) in HEK293T cells, indicating that EphA4 is a new KSHV entry receptor. To confirm that epithelial cells express EphA2 and EphA4, we analyzed the expression of EphA2 and EphA4 in epithelial cells, endothelial cells, B cells, monocytes, fibroblasts using RNA sequencing (RNA-seq) data analysis of existing data sets. We found that these cell types broadly express both EphA2 and EphA4, with the exception of monocytes and B cells. To confirm EphA4 is important for KSHV fusion and infection, we generated EphA2 and EphA4 single- and double-knockout cells. We found that both EphA2 and EphA4 play a role in KSHV fusion and infection, since EphA2-EphA4 d...Continue Reading

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Citations

Nov 23, 2019·Viruses·Stephen J Dollery
Nov 26, 2020·Nature Communications·Chao SuJinghua Yan
Jan 23, 2021·Viruses·Emma van der MeulenGeorgia Schäfer
Oct 23, 2020·Nature Reviews. Microbiology·Sarah A ConnollyRichard Longnecker
Dec 22, 2020·Frontiers in Cellular and Infection Microbiology·Farizeh Aalam, Jennifer Totonchy
Jan 13, 2021·Cancers·Meg AndertonGeorgia Schäfer
Jan 1, 2019·Current Clinical Microbiology Reports·Darin J Weed, Blossom Damania
Mar 4, 2021·PLoS Pathogens·Anna K GroßkopfAlexander S Hahn
Apr 5, 2021·Frontiers in Cellular and Infection Microbiology·Kumari Asha, Neelam Sharma-Walia

Datasets Mentioned

BETA
SRR5048157
SRR5048162
SRR5048180
SRR5048177
SRR3192540
SRR3192539
SRR3192374
SRR3192375
SRR3192370
SRR3192369

Methods Mentioned

BETA
fluorescence microscopy
flow cytometry
RNA-seq
CELISA
enzyme-linked immunosorbent assay
coimmunoprecipitation
transfection

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