Cleavage and secretion of Epstein-Barr virus glycoprotein 42 promote membrane fusion with B lymphocytes.
Epstein-Barr virus (EBV) membrane glycoprotein 42 (gp42) is required for viral entry into B lymphocytes through binding to human leukocyte antigen (HLA) class II on the B-cell surface. EBV gp42 plays multiple roles during infection, including acting as a coreceptor for viral entry into B cells, binding to EBV glycoprotein H (gH) and gL during the process of membrane fusion, and blocking T-cell recognition of HLA class II-peptide complexes through steric hindrance. EBV gp42 occurs in two forms in infected cells, a full-length membrane-bound form and a soluble form generated by proteolytic cleavage that is secreted from infected cells due to loss of the N-terminal transmembrane domain. Both the full-length and the secreted gp42 forms bind to gH/gL and HLA class II, and the functional significance of gp42 cleavage is currently unclear. We found that in a virus-free cell-cell fusion assay, enhanced secretion of gp42 promoted fusion with B lymphocytes, and mutation of the site of gp42 cleavage inhibited membrane fusion activity. The site of gp42 cleavage was found to be physically distinct from the residues of gp42 necessary for binding to gH/gL. These results suggest that cleavage and secretion of gp42 are necessary for the process of membrane fusion with B lymphocytes, providing the first indicated functional difference between full-length and cleaved, secreted gp42.
Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Jessica
J
Sorem
Theodore S
TS
Jardetzky
Richard
R
Longnecker
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008561:Membrane Fusion; D009154:Mutation; D011485:Protein Binding; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
C101688:BZLF2 protein, Herpesvirus 4, Human; D006023:Glycoproteins; D000949:Histocompatibility Antigens Class II; D014764:Viral Proteins