Academic Journal
CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release
| العنوان: | CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release |
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| المؤلفون: | 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 |
| المصدر: | eLife, Vol 8 (2019) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | CCL2, ALIX, HIV-1, HIV-1 clade C, Gag p6, late domain, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/35546; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.35546 |
| URL الوصول: | https://doaj.org/article/8d09f15a9dfc42678842893a609be729 |
| رقم الانضمام: | edsdoj.8d09f15a9dfc42678842893a609be729 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.35546 |