title: Measles virus envelope glycoproteins hetero-oligomerize in the endoplasmic reticulum.
abstract: The endoplasmic reticulum (ER) was investigated as the initial oligomerization site for the envelope glycoproteins H and F of measles virus (MV), a clinically relevant member of the Paramyxoviridae family, and consequences of this interaction for viral replication were studied. Both proteins were tagged at their cytosolic tails with RRR and KKXX motifs, respectively, resulting in their efficient retention in the ER. Co-transfection of the retained constructs with transport competent MV glycoproteins revealed a dominant negative effect on their biological activity indicating intracellular complex formation and thus retention. Pulse-chase analysis and co-immunoprecipitation experiments demonstrated that this effect is based on both homo- and hetero-oligomerization in the ER. Recombinant viruses additionally expressing ER-retained F showed an altered cytopathic phenotype accompanied by greatly reduced particle release. Similar mutant viruses additionally expressing ER-retained H could not be rescued indicating an even greater negative effect of this protein on virus viability. Our study suggests that both homo- and hetero-oligomerization of MV glycoproteins occur in the ER and that these events are of significance for early steps of particle assembly.
authors.affiliation: Molecular Medicine Program, Mayo Foundation, Rochester, Minnesota 55905, USA. plemper.richard@mayo.edu
authors.forename: R K
authors.initials: RK
authors.lastname: Plemper
authors.forename: A L
authors.initials: AL
authors.lastname: Hammond
authors.forename: R
authors.initials: R
authors.lastname: Cattaneo
mesh_terms: D000818:Animals; D001483:Base Sequence; D001704:Biopolymers; D002522:Chlorocebus aethiops; D017931:DNA Primers; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D007700:Kinetics; D008459:Measles virus / Q000378:metabolism*; D009154:Mutation; D011233:Precipitin Tests; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism*
chemical_list: D001704:Biopolymers; D017931:DNA Primers; D006023:Glycoproteins; D014759:Viral Envelope Proteins