Moesin is required for HIV-1-induced CD4-CXCR4 interaction, F-actin redistribution, membrane fusion and viral infection in lymphocytes.
The human immunodeficiency virus 1 (HIV-1) envelope regulates the initial attachment of viral particles to target cells through its association with CD4 and either CXCR4 or CCR5. Although F-actin is required for CD4 and CXCR4 redistribution, little is known about the molecular mechanisms underlying this fundamental process in HIV infection. Using CD4(+) CXCR4(+) permissive human leukemic CEM T cells and primary lymphocytes, we have investigated whether HIV-1 Env might promote viral entry and infection by activating ERM (ezrin-radixin-moesin) proteins to regulate F-actin reorganization and CD4/CXCR4 co-clustering. The interaction of the X4-tropic protein HIV-1 gp120 with CD4 augments ezrin and moesin phosphorylation in human permissive T cells, thereby regulating ezrin-moesin activation. Moreover, the association and clustering of CD4-CXCR4 induced by HIV-1 gp120 requires moesin-mediated anchoring of actin in the plasma membrane. Suppression of moesin expression with dominant-negative N-moesin or specific moesin silencing impedes reorganization of F-actin and HIV-1 entry and infection mediated by the HIV-1 envelope protein complex. Therefore, we propose that activated moesin promotes F-actin redistribution and CD4-CXCR4 clustering and is also required for efficient X4-tropic HIV-1 infection in permissive lymphocytes.
Barrero-Villar
Marta
M
Servicio de Inmunología, Hospital Universitario de La Princesa, 28006 Madrid, Spain.
Cabrero
José Román
JR
Gordón-Alonso
Mónica
M
Barroso-González
Jonathan
J
Alvarez-Losada
Susana
S
Muñoz-Fernández
M Angeles
MA
Sánchez-Madrid
Francisco
F
Valenzuela-Fernández
Agustín
A
D000199:Actins / Q000378:metabolism*; D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000821:virology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization; D000099149:Ezrin
D000199:Actins; D015704:CD4 Antigens; D003598:Cytoskeletal Proteins; D015699:HIV Envelope Protein gp120; D008565:Membrane Proteins; D008840:Microfilament Proteins; D019718:Receptors, CXCR4; D011993:Recombinant Fusion Proteins; D000099149:Ezrin; C514793:gp120 protein, Human immunodeficiency virus 1; C071058:moesin; C071776:radixin