Format

Send to

Choose Destination
Elife. 2019 Jun 7;8. pii: e35546. doi: 10.7554/eLife.35546.

CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release.

Author information

1
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States.
2
Department of Genetics, Albert Einstein College of Medicine, Bronx, United States.
3
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, United States.
4
Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, United States.
#
Contributed equally

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.

KEYWORDS:

ALIX; CCL2; Gag p6; HIV-1; HIV-1 clade C; human; infectious disease; late domain; microbiology; virus

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center