biostudies-literatureCarlson LANIBIB NIH HHSNIAID NIH HHS592-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC3454483biostudies-literatureUnknown4(6)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 spherCell host & microbeThree-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis.PMC34544835 P41 EB2181R01 AI073098P41 EB002181Briggs JACarlson LASimon MNJohnson MCMuller BGrunewald KRiches JDGlass BKrausslich HGfalseThree-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis.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 spher2008-01-01T00:00:00Z2008 Dec2025-05-29T22:30:34.808Z2019-03-27T00:58:17ZS-EPMC34544831906425910.1016/j.chom.2008.10.013