DOI: 10.1101/510651Jan 3, 2019Paper

Ephrin receptor A4 (EphA4) is a new Kaposi's sarcoma-associated herpesvirus virus entry receptor

BioRxiv : the Preprint Server for Biology
Jia ChenRichard Longnecker


Kaposi's sarcoma-associated herpesvirus (KSHV) is a human g-herpesvirus 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 our current studies, we have found that EphA4 promotes KSHV gH/gL-mediated fusion and infection better than 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-seq data analysis of existing data sets. We found 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 double knockout cells had the greatest decrease in fusion activity and infecti...Continue Reading

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Dendritic Cells
Epithelial Cells
Epstein-Barr Virus
Kaposi Sarcoma
Viral Envelope Proteins

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