title: The measles virus (MV) glycoproteins interact with cellular chaperones in the endoplasmic reticulum and MV infection upregulates chaperone expression.
abstract: The present study examines the coprecipitation of measles virus (MV) glycoproteins with host cell endoplasmic reticulum (ER) chaperone proteins. Both the haemagglutinin (H) and fusion (F) glycoproteins interacted with calnexin and GRP78, whereas interaction with calreticulin was only demonstrated for the H glycoprotein. The alpha-glucosidase inhibitor castanospermine reduced and delayed the association of F proteins with calnexin. We have previously shown that alpha-glucosidase activity is important for the functionality and antigenicity of the MV F glycoprotein and for release of MV particles from infected cells. Thus, interaction with calnexin appears vital for processing of nascent MV F protein into its functional conformation. In contrast to many other viral glycoproteins, a substantial proportion of the pulsed MV glycoproteins remained associated with ER chaperones for more than 2(1/2) h. Thus, the slow and incomplete migration of MV glycoproteins to the cell surface may result from their retention by ER chaperones, probably due to malfolding. MV infection upregulated the cellular expression of calreticulin and GRP78 and also increased their presence at the cell surface. The chaperone proteins are involved in a wide range of cellular processes, and their induction by MV may play a role for the pathogenesis of measles and its sequelae.
authors.affiliation: Department of Medical Microbiology and Immunology, Panum Institute, University of Copenhagen, Denmark. gb@kvl.dk
authors.forename: G
authors.initials: G
authors.lastname: Bolt
mesh_terms: D002135:Calcium-Binding Proteins / Q000502:physiology; D037281:Calnexin; D037282:Calreticulin; D002352:Carrier Proteins / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000821:virology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D006360:Heat-Shock Proteins; D006389:Hemagglutinins, Viral / Q000502:physiology*; D006801:Humans; D008459:Measles virus / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology*; D012261:Ribonucleoproteins / Q000502:physiology; D015854:Up-Regulation; D014760:Viral Fusion Proteins / Q000502:physiology*
chemical_list: D002135:Calcium-Binding Proteins; D037282:Calreticulin; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D006389:Hemagglutinins, Viral; D008565:Membrane Proteins; D018832:Molecular Chaperones; D012261:Ribonucleoproteins; D014760:Viral Fusion Proteins; C018551:glucose-regulated proteins; C032397:hemagglutinin protein G, measles virus; D037281:Calnexin