title: Assembly of the murine leukemia virus is directed towards sites of cell-cell contact.
abstract: We have investigated the underlying mechanism by which direct cell-cell contact enhances the efficiency of cell-to-cell transmission of retroviruses. Applying 4D imaging to a model retrovirus, the murine leukemia virus, we directly monitor and quantify sequential assembly, release, and transmission events for individual viral particles as they happen in living cells. We demonstrate that de novo assembly is highly polarized towards zones of cell-cell contact. Viruses assembled approximately 10-fold more frequently at zones of cell contact with no change in assembly kinetics. Gag proteins were drawn to adhesive zones formed by viral Env glycoprotein and its cognate receptor to promote virus assembly at cell-cell contact. This process was dependent on the cytoplasmic tail of viral Env. Env lacking the cytoplasmic tail while still allowing for contact formation, failed to direct virus assembly towards contact sites. Our data describe a novel role for the viral Env glycoprotein in establishing cell-cell adhesion and polarization of assembly prior to becoming a fusion protein to allow virus entry into cells.
authors.affiliation: Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Sherer
authors.forename: Gisela
authors.initials: G
authors.lastname: Heidecker
authors.forename: David
authors.initials: D
authors.lastname: Derse
authors.forename: Walther
authors.initials: W
authors.lastname: Mothes
mesh_terms: D000818:Animals; D019556:COS Cells; D002448:Cell Adhesion; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D015683:Gene Products, gag / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009052:Leukemia Virus, Murine / Q000378:metabolism* / Q000472:pathogenicity; D014759:Viral Envelope Proteins / Q000378:metabolism; D053585:Virus Attachment
chemical_list: D015683:Gene Products, gag; D014759:Viral Envelope Proteins