title: Three-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis.
abstract: Current models of HIV-1 morphogenesis hold that newly synthesized viral Gag polyproteins traffic to and assemble at the cell membrane into spherical protein shells. The resulting late-budding structure is thought to be released by the cellular ESCRT machinery severing the membrane tether connecting it to the producer cell. Using electron tomography and scanning transmission electron microscopy, we find that virions have a morphology and composition distinct from late-budding sites. Gag is arranged as a continuous but incomplete sphere in the released virion. In contrast, late-budding sites lacking functional ESCRT exhibited a nearly closed Gag sphere. The results lead us to propose that budding is initiated by Gag assembly, but is completed in an ESCRT-dependent manner before the Gag sphere is complete. This suggests that ESCRT functions early in HIV-1 release--akin to its role in vesicle formation--and is not restricted to severing the thin membrane tether.
authors.affiliation: Abteilung Virologie, Universitätsklinikum D-69120 Heidelberg, Germany.
authors.forename: Lars-Anders
authors.initials: LA
authors.lastname: Carlson
authors.forename: John A G
authors.initials: JA
authors.lastname: Briggs
authors.forename: Bärbel
authors.initials: B
authors.lastname: Glass
authors.forename: James D
authors.initials: JD
authors.lastname: Riches
authors.forename: Martha N
authors.initials: MN
authors.lastname: Simon
authors.forename: Marc C
authors.initials: MC
authors.lastname: Johnson
authors.forename: Barbara
authors.initials: B
authors.lastname: Müller
authors.forename: Kay
authors.initials: K
authors.lastname: Grünewald
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Kräusslich
mesh_terms: D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology* / Q000648:ultrastructure*; D015497:HIV-1 / Q000502:physiology* / Q000648:ultrastructure*; D006367:HeLa Cells; D006801:Humans; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D014771:Virion / Q000648:ultrastructure*; D019065:Virus Assembly; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D054301:gag Gene Products, Human Immunodeficiency Virus