Gelsolin activity controls efficient early HIV-1 infection

HIV-1 entry into target lymphocytes requires the activity of actin adaptors that stabilize and reorganize cortical F-actin, like moesin and filamin-A. These alterations are necessary for the redistribution of CD4-CXCR4/CCR5 to one pole of the cell, a process that increases the probability of HIV-1 E...

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Published in:Retrovirology 2013-04, Vol.10 (1), p.39-39, Article 39
Main Authors: García-Expósito, Laura, Ziglio, Serena, Barroso-González, Jonathan, de Armas-Rillo, Laura, Valera, María-Soledad, Zipeto, Donato, Machado, José-David, Valenzuela-Fernández, Agustín
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
Actin
Actins - antagonists & inhibitors
AIDS
Antiviral Agents - metabolism
Antiviral Agents - therapeutic use
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - virology
Cell Line
Control
Cytoskeleton
Flow cytometry
Gelsolin - metabolism
Health aspects
HIV
HIV (Viruses)
HIV-1 - immunology
HIV-1 - physiology
Human immunodeficiency virus
Human immunodeficiency virus 1
Humans
Infections
Lymphocytes
Medicine
Muscle proteins
Pharmacology
Proteins
Receptors, HIV - antagonists & inhibitors
Signal Transduction
Virus diseases
Virus Internalization
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Summary:HIV-1 entry into target lymphocytes requires the activity of actin adaptors that stabilize and reorganize cortical F-actin, like moesin and filamin-A. These alterations are necessary for the redistribution of CD4-CXCR4/CCR5 to one pole of the cell, a process that increases the probability of HIV-1 Envelope (Env)-CD4/co-receptor interactions and that generates the tension at the plasma membrane necessary to potentiate fusion pore formation, thereby favouring early HIV-1 infection. However, it remains unclear whether the dynamic processing of F-actin and the amount of cortical actin available during the initial virus-cell contact are required to such events. Here we show that gelsolin restructures cortical F-actin during HIV-1 Env-gp120-mediated signalling, without affecting cell-surface expression of receptors or viral co-receptor signalling. Remarkably, efficient HIV-1 Env-mediated membrane fusion and infection of permissive lymphocytes were impaired when gelsolin was either overexpressed or silenced, which led to a loss or gain of cortical actin, respectively. Indeed, HIV-1 Env-gp120-induced F-actin reorganization and viral receptor capping were impaired under these experimental conditions. Moreover, gelsolin knockdown promoted HIV-1 Env-gp120-mediated aberrant pseudopodia formation. These perturbed-actin events are responsible for the inhibition of early HIV-1 infection. For the first time we provide evidence that through its severing of cortical actin, and by controlling the amount of actin available for reorganization during HIV-1 Env-mediated viral fusion, entry and infection, gelsolin can constitute a barrier that restricts HIV-1 infection of CD4+ lymphocytes in a pre-fusion step. These findings provide important insights into the complex molecular and actin-associated dynamics events that underlie early viral infection. Thus, we propose that gelsolin is a new factor that can limit HIV-1 infection acting at a pre-fusion step, and accordingly, cell-signals that regulate gelsolin expression and/or its actin-severing activity may be crucial to combat HIV-1 infection.
ISSN:1742-4690
1742-4690
DOI:10.1186/1742-4690-10-39