CCL2 mobilizes ALIX to facilitate Gag-p6 mediated HIV-1 virion release.
Elife
; 82019 06 07.
Article
em En
| MEDLINE
| ID: mdl-31172941
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação ao Cálcio
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HIV-1
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Proteínas de Ciclo Celular
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Quimiocina CCL2
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Produtos do Gene gag do Vírus da Imunodeficiência Humana
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Interações Hospedeiro-Patógeno
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Complexos Endossomais de Distribuição Requeridos para Transporte
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Liberação de Vírus
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article