Rhesus Monkey Rhadinovirus Uses Eph Family Receptors for Entry into B Cells and Endothelial Cells but Not Fibroblasts

Alexander S. Hahn, Ronald Charles Desrosiers

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Cellular Ephrin receptor tyrosine kinases (Ephrin receptors, Ephs) were found to interact efficiently with the gH/gL glycoprotein complex of the rhesus monkey rhadinovirus (RRV). Since EphA2 was recently identified as a receptor for the Kaposi's sarcoma-associated herpesvirus (KSHV) (Hahn et al., Nature Medicine 2012), we analyzed RRV and KSHV in parallel with respect to Eph-binding and Eph-dependent entry. Ten of the 14 Eph proteins, including both A- and B-type, interacted with RRV gH/gL. Two RRV strains with markedly different gH/gL sequences exhibited similar but slightly different binding patterns to Ephs. gH/gL of KSHV displayed high affinity towards EphA2 but substantially weaker binding to only a few other Ephs of the A-type. Productive entry of RRV 26-95 into B cells and into endothelial cells was essentially completely dependent upon Ephs since expression of a GFP reporter cassette from recombinant virus could be blocked to greater than 95% by soluble Eph decoys using these cells. In contrast, entry of RRV into fibroblasts and epithelial cells was independent of Ephs by these same criteria. Even high concentrations and mixtures of soluble Eph decoys were not able to reduce by any appreciable extent the number of fibroblasts and epithelial cells productively entered by RRV. Thus, RRV is similar to its close relative KSHV in the use of Eph family receptors for productive entry into B cells and endothelial cells. However, RRV uses a separate, distinct, Eph-independent pathway for productive entry into fibroblasts and epithelial cells. Whether KSHV also uses an Eph-independent pathway in some circumstances or to some extent remains to be determined.

Original languageEnglish (US)
Article numbere1003360
JournalPLoS Pathogens
Volume9
Issue number5
DOIs
StatePublished - May 2013
Externally publishedYes

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Rhadinovirus
Eph Family Receptors
Macaca mulatta
B-Lymphocytes
Endothelial Cells
Fibroblasts
Human Herpesvirus 8
Epithelial Cells
Receptor Protein-Tyrosine Kinases
Glycoproteins
Medicine

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Rhesus Monkey Rhadinovirus Uses Eph Family Receptors for Entry into B Cells and Endothelial Cells but Not Fibroblasts. / Hahn, Alexander S.; Desrosiers, Ronald Charles.

In: PLoS Pathogens, Vol. 9, No. 5, e1003360, 05.2013.

Research output: Contribution to journalArticle

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