Fusion of epithelial cells by Epstein-Barr virus proteins is triggered by binding of viral glycoproteins gHgL to integrins alphavbeta6 or alphavbeta8.
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is causally implicated in the development of lymphoid and epithelial tumors. Entry of virus requires fusion of virus envelopes and cell membranes. Fusion with B lymphocytes requires virus glycoprotein gB and a 3-part complex of glycoproteins, gHgLgp42. It is triggered by interactions between glycoprotein 42 (gp42) and HLA class II. However, fusion with epithelial cells is impeded by gp42 and instead is triggered by interactions between an unknown epithelial protein and a 2-part complex of gHgL. We report here that gHgL binds with high affinity to epithelial cells and that affinity of binding is increased by 3 orders of magnitude in the presence of Mn(2+). Binding and infection can be reduced by fibronectin and vitronectin, by down-regulation of integrin alphav, or by a peptide corresponding to 13 aa of gH which include a KGDE motif. Fusion of cells expressing gB and gHgL can be blocked by vitronectin or triggered by addition of soluble truncated integrins alphavbeta6 and alphavbeta8. We conclude that the direct interaction between EBV gHgL and integrins alphavbeta6 and alphavbeta8 can provide the trigger for fusion of EBV with an epithelial cell.
Chesnokova
Liudmila S
LS
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
Nishimura
Stephen L
SL
Hutt-Fletcher
Lindsey M
LM
D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology; D015153:Blotting, Western; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000378:metabolism*; D005353:Fibronectins / Q000494:pharmacology; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D008345:Manganese / Q000494:pharmacology*; D034622:RNA Interference; D014760:Viral Fusion Proteins / Q000378:metabolism*; D053586:Virus Internalization / Q000187:drug effects*; D019096:Vitronectin / Q000494:pharmacology
D005353:Fibronectins; D000949:Histocompatibility Antigens Class II; D016023:Integrins; D014760:Viral Fusion Proteins; D019096:Vitronectin; C403414:integrin alphavbeta8; D008345:Manganese