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CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release.
- Source :
-
ELife [Elife] 2019 Jun 07; Vol. 8. Date of Electronic Publication: 2019 Jun 07. - Publication Year :
- 2019
-
Abstract
- Cellular ESCRT machinery plays pivotal role in HIV-1 budding and release. Extracellular stimuli that modulate HIV-1 egress are currently unknown. We found that CCL2 induced by HIV-1 clade B (HIV-1B) infection of macrophages enhanced virus production, while CCL2 immuno-depletion reversed this effect. Additionally, HIV-1 clade C (HIV-1C) was refractory to CCL2 levels. We show that CCL2-mediated increase in virus production requires Gag late motif LYPX present in HIV-1B, but absent in HIV-1C, and ALIX protein that recruits ESCRT III complex. CCL2 immuno-depletion sequestered ALIX to F-actin structures, while CCL2 addition mobilized it to cytoplasm facilitating Gag-ALIX binding. The LYPX motif improves virus replication and its absence renders the virus less fit. Interestingly, novel variants of HIV-1C with PYRE/PYKE tetrapeptide insertions in Gag-p6 conferred ALIX binding, CCL2-responsiveness and enhanced virus replication. These results, for the first time, indicate that CCL2 mediates ALIX mobilization from F-actin and enhances HIV-1 release and fitness.<br />Competing Interests: DA, VR, XW, SR, MP, AR, AF, AB, GK, VP No competing interests declared
- Subjects :
- Cells, Cultured
Humans
Macrophages virology
Calcium-Binding Proteins metabolism
Cell Cycle Proteins metabolism
Chemokine CCL2 metabolism
Endosomal Sorting Complexes Required for Transport metabolism
HIV-1 growth & development
Host-Pathogen Interactions
Virus Release
gag Gene Products, Human Immunodeficiency Virus metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 31172941
- Full Text :
- https://doi.org/10.7554/eLife.35546