AP-3 directs the intracellular trafficking of HIV-1 Gag and plays a key role in particle assembly.
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.
Dong
Xinhong
X
Department of Pediatrics and Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
Li
Hua
H
Derdowski
Aaron
A
Ding
Lingmei
L
Burnett
Atuhani
A
Chen
Xuemin
X
Peters
Timothy R
TR
Dermody
Terence S
TS
Woodruff
Elvin
E
Wang
Jaang-Jiun
JJ
Spearman
Paul
P
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*
D033963:Adaptor Protein Complex 3; D033981:Adaptor Protein Complex delta Subunits; D015683:Gene Products, gag; D021122:Protein Subunits