title: Epstein-Barr virus glycoprotein gB and gHgL can mediate fusion and entry in trans, and heat can act as a partial surrogate for gHgL and trigger a conformational change in gB.
abstract: Epstein-Barr virus (EBV) fusion with an epithelial cell requires virus glycoproteins gHgL and gB and is triggered by an interaction between gHgL and integrin αvβ5, αvβ6, or αvβ8. Fusion with a B cell requires gHgL, gp42, and gB and is triggered by an interaction between gp42 and human leukocyte antigen class II. We report here that, like alpha- and betaherpesviruses, EBV, a gammaherpesvirus, can mediate cell fusion if gB and gHgL are expressed in trans. Entry of a gH-null virus into an epithelial cell is possible if the epithelial cell expresses gHgL, and entry of the same virus, which phenotypically lacks gHgL and gp42, into a B cell expressing gHgL is possible in the presence of a soluble integrin. Heat is capable of inducing the fusion of cells expressing only gB, and the proteolytic digestion pattern of gB in virions changes in the same way following the exposure of virus to heat or to soluble integrins. It is suggested that the Gibbs free energy released as a result of the high-affinity interaction of gHgL with an integrin contributes to the activation energy required to cause the refolding of gB from a prefusion to a postfusion conformation.
  
  
  OBJECTIVE
  The core fusion machinery of herpesviruses consists of glycoproteins gB and gHgL. We demonstrate that as in alpha- and betaherpesvirus, gB and gHgL of the gammaherpesvirus EBV can mediate fusion and entry when expressed in trans in opposing membranes, implicating interactions between the ectodomains of the proteins in the activation of fusion. We further show that heat and exposure to a soluble integrin, both of which activate fusion, result in the same changes in the proteolytic digestion pattern of gB, possibly representing the refolding of gB from its prefusion to its postfusion conformation.
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
authors.forename: Liudmila S
authors.initials: LS
authors.lastname: Chesnokova
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
authors.forename: Munish K
authors.initials: MK
authors.lastname: Ahuja
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA lhuttf@lsuhsc.edu.
authors.forename: Lindsey M
authors.initials: LM
authors.lastname: Hutt-Fletcher
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000821:virology; D002460:Cell Line; D004854:Herpesvirus 4, Human / Q000502:physiology* / Q000528:radiation effects; D006358:Hot Temperature; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D011487:Protein Conformation; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D053586:Virus Internalization / Q000528:radiation effects*
chemical_list: D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C090195:glycoprotein 85, Epstein-Barr virus; C558483:glycoprotein B, human herpesvirus 4; C103802:glycoprotein L, Human herpesvirus 4