Identification of an intracellular trafficking and assembly pathway for HIV-1 Gag Journal Article
| Authors: | Perlman, M.; Resh, M. D. |
| Article Title: | Identification of an intracellular trafficking and assembly pathway for HIV-1 Gag |
| Abstract: | Retroviral Gag proteins are membrane-bound polyproteins that are necessary and sufficient for virus-like particle (VLP) formation. It is not known how Gag traffics through the cell or how the site of particle production is determined. Here we use two techniques, biarsenical/ tetracysteine (TC) labeling and release from a cycloheximide block, to follow the trafficking of newly synthesized HIV-1 Gag. Gag first appears diffusely distributed in the cytosol, accumulates in perinuclear clusters, passes transiently through a multivesicular body (MVB)-like compartment, and then travels to the plasma membrane (PM). Sequential passage of Gag through these temporal intermediates was confirmed by live cell imaging. Induction of a transient rise in cytoplasmic calcium increased the amounts of Gag, Gag assembly intermediates and VLPs in MVBs, and resulted in a dramatic increase in VLP release. These results define an intracellular trafficking pathway for HIV-1 Gag that uses perinuclear compartments and the MVB as trafficking intermediates. We propose that the regulation of Gag association with MVB-like compartments regulates the site of HIV-1 budding and particle formation. © Blackwell Munksgaard, 2006. |
| Keywords: | controlled study; human cell; nonhuman; protein localization; animal cell; animals; microscopy, electron; cell compartmentalization; image analysis; protein assembly; green fluorescent protein; fluorescent dyes; intracellular transport; hela cells; transfection; cercopithecus aethiops; cos cells; arsenicals; regulatory mechanism; protein synthesis; membrane protein; cell membrane; protein transport; protein secretion; cytoplasm; base sequence; dna, viral; virus particle; calcium cell level; cytosol; retrovirus; human immunodeficiency virus 1; hiv-1; virus protein; exocytosis; virus assembly; ionomycin; protein aggregation; calcium transport; calcium signaling; calcium ion; membranes; gag protein; cycloheximide; gag; gene products, gag; protein synthesis inhibitors; cd63 antigen; multivesicular body/exocytosis; viral particle assembly; secretory vesicle |
| Journal Title: | Traffic |
| Volume: | 7 |
| Issue: | 6 |
| ISSN: | 1398-9219 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2006-06-01 |
| Start Page: | 731 |
| End Page: | 745 |
| Language: | English |
| DOI: | 10.1111/j.1398-9219.2006.00428.x |
| PUBMED: | 16683918 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 79" - "Export Date: 4 June 2012" - "CODEN: TRAFF" - "Source: Scopus" |
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