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CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release
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....
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592687/ https://www.ncbi.nlm.nih.gov/pubmed/31172941 http://dx.doi.org/10.7554/eLife.35546 |
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author | 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 |
author_facet | 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 |
author_sort | Ajasin, David O |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6592687 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-65926872019-06-26 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 eLife Microbiology and Infectious Disease 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. eLife Sciences Publications, Ltd 2019-06-07 /pmc/articles/PMC6592687/ /pubmed/31172941 http://dx.doi.org/10.7554/eLife.35546 Text en http://creativecommons.org/publicdomain/zero/1.0/ http://creativecommons.org/publicdomain/zero/1.0/This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (http://creativecommons.org/publicdomain/zero/1.0/) . |
spellingShingle | Microbiology and Infectious Disease 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 |
title | CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release |
title_full | CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release |
title_fullStr | CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release |
title_full_unstemmed | CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release |
title_short | CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release |
title_sort | ccl2 mobilizes alix to facilitate gag-p6 mediated hiv-1 virion release |
topic | Microbiology and Infectious Disease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592687/ https://www.ncbi.nlm.nih.gov/pubmed/31172941 http://dx.doi.org/10.7554/eLife.35546 |
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