Cell-surface expression of a mutated Epstein–Barr virus glycoprotein B allows fusion independent of other viral proteins

doi:10.1073/pnas.0404535101

Cell-surface expression of a mutated Epstein–Barr virus glycoprotein B allows fusion independent of other viral proteins

Department of Microbiology and Immunology, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611

Edited by Elliott D. Kieff, Harvard University, Boston, MA, and approved November 5, 2004 (received for review June 24, 2004)

Abstract

Epstein–Barr virus (EBV) infects human B lymphocytes and epithelial cells. We have compared the requirements for EBV glycoprotein-induced cell fusion between Chinese hamster ovary effecter cells and human B lymphoblasts or epithelial cells by using a virus-free cell fusion assay. EBV-encoded gB, gH, gL, and gp42 glycoproteins were required for efficient B cell fusion, whereas EBV gB, gH, and gL glycoproteins were required for Chinese hamster ovary effecter cell fusion with epithelial cell lines (AGS and SCC68) or the human embryonic kidney cell line 293-P. Fusion with human embryonic kidney 293-P cells was greater than fusion observed with B cells, indicative of an important role for cell contact. An antibody directed against the gH and gL complex inhibited epithelial cell fusion. Increased surface expression of gB alone as a result of truncations or point mutants in the carboxyl-terminal tail allowed gB-mediated fusion with epithelial cells, albeit at a lower level than with coexpression of gB, gH, and gL. Overall, gB appears to be the critical component for EBV glycoprotein-mediated cell fusion.

Footnotes

↵ * To whom correspondence should be addressed at: The Feinberg School of Medicine, Northwestern University, Department of Microbiology and Immunology, Ward 6-231, 303 East Chicago Avenue, Chicago, IL 60611. E-mail: r-longnecker{at}northwestern.edu.
Author contributions: M.P.M. and R.L. designed research; M.P.M. performed research; M.P.M. contributed new reagents/analytic tools; M.P.M. and R.L. analyzed data; and M.P.M. and R.L. wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: HHV, human herpesvirus; HSV, herpes simplex virus; ER, endoplasmic reticulum; EBV, Epstein–Barr virus; HEK, human embryonic kidney; CHO, Chinese hamster ovary.