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....
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/35546 |
| _version_ | 1828221784560762880 |
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| author | 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 |
| author_facet | 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 |
| author_sort | David O Ajasin |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T16:45:20Z |
| format | Article |
| id | doaj.art-8d09f15a9dfc42678842893a609be729 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:45:20Z |
| publishDate | 2019-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-8d09f15a9dfc42678842893a609be7292022-12-22T03:24:36ZengeLife Sciences Publications LtdeLife2050-084X2019-06-01810.7554/eLife.35546CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion releaseDavid O Ajasin0https://orcid.org/0000-0003-1061-1860Vasudev R Rao1https://orcid.org/0000-0002-9435-4023Xuhong Wu2Santhamani Ramasamy3Mario Pujato4Arthur P Ruiz5Andras Fiser6Anne R Bresnick7Ganjam V Kalpana8Vinayaka R Prasad9https://orcid.org/0000-0002-9461-0189Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Genetics, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Genetics, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United StatesCellular 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.https://elifesciences.org/articles/35546CCL2ALIXHIV-1HIV-1 clade CGag p6late domain |
| spellingShingle | 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 CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release eLife CCL2 ALIX HIV-1 HIV-1 clade C Gag p6 late domain |
| 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 | CCL2 ALIX HIV-1 HIV-1 clade C Gag p6 late domain |
| url | https://elifesciences.org/articles/35546 |
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