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

David O. Ajasin, Vasudev R. Rao, Xuhong Wu, Santhamani Ramasamy, Mario Pujato, Arthur P. Ruiz, Andras Fiser, Anne R. Bresnick, Ganjam V. Kalpana, Vinayaka R. Prasad

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournaleLife
Volume8
DOIs
StatePublished - Jun 7 2019

Fingerprint

Viruses
Virion
HIV-1
Endosomal Sorting Complexes Required for Transport
Actins
Virus Replication
Macrophages
Refractory materials
Protein C
Cytoplasm
Proteins
Infection

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Ajasin, D. O., Rao, V. R., Wu, X., Ramasamy, S., Pujato, M., Ruiz, A. P., ... Prasad, V. R. (2019). CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release. eLife, 8. https://doi.org/10.7554/eLife.35546

CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release. / Ajasin, David O.; Rao, Vasudev R.; Wu, Xuhong; Ramasamy, Santhamani; Pujato, Mario; Ruiz, Arthur P.; Fiser, Andras; Bresnick, Anne R.; Kalpana, Ganjam V.; Prasad, Vinayaka R.

In: eLife, Vol. 8, 07.06.2019.

Research output: Contribution to journalArticle

Ajasin DO, Rao VR, Wu X, Ramasamy S, Pujato M, Ruiz AP et al. CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release. eLife. 2019 Jun 7;8. https://doi.org/10.7554/eLife.35546
Ajasin, David O. ; Rao, Vasudev R. ; Wu, Xuhong ; Ramasamy, Santhamani ; Pujato, Mario ; Ruiz, Arthur P. ; Fiser, Andras ; Bresnick, Anne R. ; Kalpana, Ganjam V. ; Prasad, Vinayaka R. / CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release. In: eLife. 2019 ; Vol. 8.
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