RT info:eu-repo/semantics/article
T1 Moesin is required for HIV-1-induced CD4-CXCR4 interaction, F-actin redistribution, membrane fusion and viral infection in lymphocytes.
A1 Valenzuela Fernández, Agustín
A1 Barrero Villar, Marta
A1 Cabrero, José Román
A1 Gordón Alonso, Mónica
A1 Barroso González, Jonathan
A1 Álvarez Losada, Susana
A1 Muñoz Fernández, M. Ángeles
A1 Sánchez Madrid, Francisco
A2 Medicina Física y Farmacología
A2 Grupo "inmunología Celular y Viral".
K1 ERM
K1 Ezrin-radixin-moesin
K1 F-actin redistribution
K1 CD4-CXCR4 interaction
K1 HIV-1 infection and entry
AB The human immunodeficiency virus 1 (HIV-1) enveloperegulates the initial attachment of viral particles to target cellsthrough its association with CD4 and either CXCR4 or CCR5.Although F-actin is required for CD4 and CXCR4redistribution, little is known about the molecular mechanismsunderlying this fundamental process in HIV infection. UsingCD4+ CXCR4+ permissive human leukemic CEM T cells andprimary lymphocytes, we have investigated whether HIV-1 Envmight promote viral entry and infection by activating ERM(ezrin-radixin-moesin) proteins to regulate F-actinreorganization and CD4/CXCR4 co-clustering. The interactionof the X4-tropic protein HIV-1 gp120 with CD4 augments ezrinand moesin phosphorylation in human permissive T cells,thereby regulating ezrin-moesin activation. Moreover, theassociation and clustering of CD4-CXCR4 induced by HIV-1gp120 requires moesin-mediated anchoring of actin in theplasma membrane. Suppression of moesin expression withdominant-negative N-moesin or specific moesin silencingimpedes reorganization of F-actin and HIV-1 entry and infectionmediated by the HIV-1 envelope protein complex. Therefore,we propose that activated moesin promotes F-actinredistribution and CD4-CXCR4 clustering and is also requiredfor efficient X4-tropic HIV-1 infection in permissivelymphocytes.
YR 2009
FD 2009
LK http://riull.ull.es/xmlui/handle/915/35368
UL http://riull.ull.es/xmlui/handle/915/35368
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 05-jul-2024