HIV infection of T cells: actin-in and actin-out.
Three studies shed light on the decade-old observation that the actin cytoskeleton is hijacked to facilitate entry of HIV into its target cells. Polymerization of actin is required to assemble high concentrations of CD4 and CXCR4 at the plasma membrane, which promote viral binding and entry in both the simple model of infection by free virus and the more physiologically relevant route of infection through the virological synapse. Three types of actin-interacting proteins-filamin, ezrin/radixin/moesin (ERM), and cofilin-are now shown to play critical roles in this process. Filamin binds to both CD4 and CXCR4 in a manner promoted by signaling of the HIV gp120 glycoprotein. ERM proteins attach actin filaments to the membrane and may promote polymerization of actin. Early in the process of viral entry, cofilin is inactivated, which is proposed to facilitate the early assembly of actin filaments, but cofilin is reported to be activated soon thereafter to facilitate postentry events. This complex role of cofilin may help to reconcile the paradox that actin polymerization promotes initial binding and fusion steps but inhibits some subsequent early postentry events.
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Yin
Y
Liu
Natalya V
NV
Belkina
Stephen
S
Shaw
D000199:Actins / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D003285:Contractile Proteins / Q000378:metabolism; D064448:Filamins; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000378:metabolism* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology
D000199:Actins; D015704:CD4 Antigens; D003285:Contractile Proteins; D064448:Filamins; D015699:HIV Envelope Protein gp120; D008840:Microfilament Proteins; D019718:Receptors, CXCR4