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The Elucidation of the Role of Arp2/3 in HIV-1 Replication in CD4 T Cells

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dc.contributor.advisor Wu, Yuntao Spear, Mark Rex
dc.creator Spear, Mark Rex en_US 2015-02-12T02:59:15Z 2015-02-12T02:59:15Z 2014 en_US
dc.description.abstract HIV-1-initiated receptor signaling and early actin dynamics are required for viral infection of resting CD4 T cells. WAVE2 is a component of a multiprotein complex linking receptor signaling to actin dynamics. WAVE2 directly activates Arp2/3, leading to actin nucleation and filament branching. Here we report that binding of HIV-1 to resting CD4 T cells and primary macrophages induces a rapid phosphorylation of WAVE2 at serine 351. This phosphorylation involves both Gαi-dependent and -independent pathways, and occurs in response to R5 and X4 viruses, suggesting that this signaling event is likely conserved in HIV infection. In addition, inhibition of WAVE2-mediated Apr2/3 activity through a specific Apr2/3 inhibitor, CK-548, inhibits both T cell chemotaxis and HIV-1 infection of CD4 T cells. Furthermore, inhibition of Arp2/3 through stable shRNA knockdown of Arp3 also inhibits HIV-1 infection of CD4 T cells. The inhibition is mainly at the level of viral nuclear migration. Our results suggest that WAVE2 and Arp2/3 are actively engaged by HIV-1 following viral binding, and that WAVE2-mediated Arp2/3 activity plays a critical role in mediating actin-based post-entry nuclear migration.
dc.format.extent 142 pages en_US
dc.language.iso en en_US
dc.rights Copyright 2014 Mark Rex Spear en_US
dc.subject Virology en_US
dc.subject Immunology en_US
dc.subject Molecular biology en_US
dc.subject Actin en_US
dc.subject Arp2/3 en_US
dc.subject HIV en_US
dc.subject WAVE2 en_US
dc.title The Elucidation of the Role of Arp2/3 in HIV-1 Replication in CD4 T Cells en_US
dc.type Dissertation en Doctoral en Biosciences en George Mason University en

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