Resting B cells as a transfer vehicle for Epstein-Barr virus infection of epithelial cells.
Epstein-Barr virus (EBV), an orally transmitted herpesvirus, efficiently targets B lymphocytes through binding of the viral envelope glycoprotein gp350 to the complement receptor CD21. How the virus accesses epithelial cells is less well understood, because such cells are largely resistant to infection with cell-free virus in vitro. Here, we show that, after binding to primary B cells, most Epstein-Barr virions are not internalized but remain on the B cell surface and from there can transfer efficiently to CD21-negative epithelial cells, increasing epithelial infection by 10(3)- to 10(4)-fold compared with cell-free virus. Transfer infection is associated with the formation of B cell-epithelial conjugates with gp350/CD21 complexes focused at the intercellular synapse; transfer involves the gp85 and gp110 viral glycoproteins but is independent of gp42, the HLA class II ligand that is essential for B cell entry. Therefore, through efficient binding to the B cell surface, EBV has developed a means of simultaneously accessing both lymphoid and epithelial compartments; in particular, infection of pharyngeal epithelium by orally transmitted virus becomes independent of initial virus replication in the B cell system.
Shannon-Lowe
C D
CD
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Birmingham B15 2TT, United Kingdom.
Neuhierl
B
B
Baldwin
G
G
Rickinson
A B
AB
Delecluse
H-J
HJ
D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology / Q000821:virology; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000821:virology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014759:Viral Envelope Proteins / Q000378:metabolism; D014771:Virion / Q000378:metabolism
D014759:Viral Envelope Proteins