title: AP-3 directs the intracellular trafficking of HIV-1 Gag and plays a key role in particle assembly.
abstract: Gag proteins direct the process of retroviral particle assembly and form the major protein constituents of the viral core. The matrix region of the HIV-1 Gag polyprotein plays a critical role in the transport of Gag to the plasma membrane assembly site. Recent evidence indicates that Gag trafficking to late endosomal compartments, including multivesicular bodies, occurs prior to viral particle budding from the plasma membrane. Here we demonstrate that the matrix region of HIV-1 Gag interacts directly with the delta subunit of the AP-3 complex, and that this interaction plays an important functional role in particle assembly. Disruption of this interaction eliminated Gag trafficking to multivesicular bodies and diminished HIV particle formation. These studies illuminate an early step in retroviral particle assembly and provide evidence that the trafficking of Gag to late endosomes is part of a productive particle assembly pathway.
authors.affiliation: Department of Pediatrics and Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Xinhong
authors.initials: X
authors.lastname: Dong
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Aaron
authors.initials: A
authors.lastname: Derdowski
authors.forename: Lingmei
authors.initials: L
authors.lastname: Ding
authors.forename: Atuhani
authors.initials: A
authors.lastname: Burnett
authors.forename: Xuemin
authors.initials: X
authors.lastname: Chen
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Peters
authors.forename: Terence S
authors.initials: TS
authors.lastname: Dermody
authors.forename: Elvin
authors.initials: E
authors.lastname: Woodruff
authors.forename: Jaang-Jiun
authors.initials: JJ
authors.lastname: Wang
authors.forename: Paul
authors.initials: P
authors.lastname: Spearman
mesh_terms: D033963:Adaptor Protein Complex 3 / Q000378:metabolism*; D033981:Adaptor Protein Complex delta Subunits / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology; D015683:Gene Products, gag / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D046529:Microscopy, Electron, Transmission; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D022161:Transport Vesicles / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D019065:Virus Assembly / Q000502:physiology*
chemical_list: D033963:Adaptor Protein Complex 3; D033981:Adaptor Protein Complex delta Subunits; D015683:Gene Products, gag; D021122:Protein Subunits