CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31172941.
- Also identified by DOI 10.7554/eLife.35546 and PMC identifier 6592687.
- Licence recorded as CC0.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Calcium-Binding Proteins
- Cell Cycle Proteins
- Chemokine CCL2
- Endosomal Sorting Complexes Required for Transport
- HIV-1
- Host-Pathogen Interactions
- Virus Release
- gag Gene Products, Human Immunodeficiency Virus