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

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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 immunodepletion 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 immunodepletion 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)
Article numbere35546
Publication statusPublished - Jun 2019


ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(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, [e35546].