RT info:eu-repo/semantics/article
T1 Gelsolin activity controls efficient early HIV-1 infection.
A1 Valenzuela Fernández, Agustín
A1 García-Expósito, L.
A1 Ziglio, S.
A1 Barroso-González, J.
A1 de Armas-Rillo, L.
A1 Valera, M.-S.
A1 Zipeto, D.
A1 Machado, J.-D.
K1 Gelsolin
K1 Actin-severing activity
K1 Perturbed-actin dynamics and receptors clustering
K1 Inhibition of early HIV-1 infection
AB Background: 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.Results: 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.Conclusions: 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. © 2013 García-Expósito et al.; licensee BioMed Central Ltd.
SN 1742-4690
YR 2013
FD 2013
LK http://riull.ull.es/xmlui/handle/915/35329
UL http://riull.ull.es/xmlui/handle/915/35329
DS Repositorio institucional de la Universidad de La Laguna
RD 10-may-2024