Human immunodeficiency virus type 1 Gag contains a dileucine-like motif that regulates association with multivesicular bodies Journal Article
| Authors: | Lindwasser, O. W.; Resh, M. D. |
| Article Title: | Human immunodeficiency virus type 1 Gag contains a dileucine-like motif that regulates association with multivesicular bodies |
| Abstract: | Multivesicular bodies (MVBs) are cholesterol-enriched organelles formed by the endocytic pathway. The topology of vesicle formation in MVBs is identical to that of retroviral budding from the plasma membrane, and budding of human immunodeficiency virus type 1 (HIV-1) into MVBs in macrophages has recently been visualized. The Gag proteins from HIV-1, as well as many other retroviruses, contain short motifs that mediate interactions with MVBs and other endocytic components, suggesting that Gag proteins directly interface with the endocytic pathway. Here, we show that HIV-1 Gag contains an internalization signal that promotes endocytosis of a chimeric transmembrane fusion protein. Mutation of this motif within Gag strongly inhibits virus-like particle production. Moreover, wild-type Gag, but not the internalization-defective mutation, can be induced to accumulate within CD63-positive MVBs by treatment of cells with U18666A, a drug that redistributes cholesterol from the plasma membrane to MVBs. We propose that HIV-1 Gag contains a signal that promotes interaction with the cellular endocytic machinery and that the site of particle production is regulated by the subcellular distribution of cholesterol. |
| Keywords: | signal transduction; controlled study; mutation; nonhuman; protein motif; animal cell; animals; cos cells; amino acid sequence; molecular sequence data; hybrid protein; cell membrane; protein transport; cellular distribution; cholesterol; macrophage; leucine; endocytosis; virus particle; cell organelle; internalization; retrovirus; human immunodeficiency virus 1; amino acid motifs; hiv-1; organelles; chimeric protein; protein lipid interaction; gag protein; virion; gene products, gag; cd63 antigen; multivesicular body; priority journal; article; 3beta (2 diethylaminoethoxy)androst 5 en 17 one; gene products, env |
| Journal Title: | Journal of Virology |
| Volume: | 78 |
| Issue: | 11 |
| ISSN: | 0022-538X |
| Publisher: | American Society for Microbiology |
| Date Published: | 2004-06-01 |
| Start Page: | 6013 |
| End Page: | 6023 |
| Language: | English |
| DOI: | 10.1128/jvi.78.11.6013-6023.2004 |
| PROVIDER: | scopus |
| PMCID: | PMC415809 |
| PUBMED: | 15140999 |
| DOI/URL: | |
| Notes: | J. Virol. -- Cited By (since 1996):40 -- Export Date: 16 June 2014 -- CODEN: JOVIA -- Source: Scopus |
