Article

AP-3 directs the intracellular trafficking of HIV-1 Gag and plays a key role in particle assembly.

Department of Pediatrics and Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
Cell (impact factor: 32.4). 04/2005; 120(5):663-74. DOI:10.1016/j.cell.2004.12.023 pp.663-74
Source: PubMed

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.

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Keywords

AP-3 complex
 
critical role
 
delta subunit
 
endosomal compartments
 
functional role
 
Gag trafficking
 
HIV particle formation
 
HIV-1 Gag interacts
 
HIV-1 Gag polyprotein
 
major protein constituents
 
matrix region
 
multivesicular bodies
 
particle assembly
 
plasma membrane
 
plasma membrane assembly site
 
productive particle assembly pathway
 
Recent evidence
 
retroviral particle assembly
 
viral core
 
viral particle