dc.creator | Carnes, Stephanie Kaye | |
dc.date.accessioned | 2020-08-21T21:16:10Z | |
dc.date.available | 2019-03-20 | |
dc.date.issued | 2019-03-20 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-03192019-104804 | |
dc.identifier.uri | http://hdl.handle.net/1803/10915 | |
dc.description.abstract | HIV-1 infection depends on efficient intracytoplasmic transport of the incoming viral core to the target cell nucleus. Evidence suggests that this movement is facilitated by the microtubule motor dynein, a large multi-protein complex that interacts with dynactin and cargo-specific adaptor proteins for retrograde movement via microtubules. Dynein adaptor proteins are necessary for activating dynein movement and for linking specific cargoes to dynein. I hypothesized that HIV-1 engages the dynein motor complex via an adaptor for intracellular transport. Here, I show that siRNA depletion of the dynein heavy chain, components of the dynactin complex, and the dynein adaptor BICD2, reduced cell permissiveness to HIV-1 infection. Cell depletion of dynein heavy chain and BICD2 resulted in impaired HIV-1 DNA accumulation in the nucleus and decreased retrograde movement of the virus. Biochemical studies revealed that dynein components and BICD2 associate with capsid-like assemblies of the HIV-1 CA protein in cell extracts and that purified recombinant BICD2 binds to CA assemblies in vitro. Association of dynein with CA assemblies was reduced upon immunodepletion of BICD2 from cell extracts. I conclude that BICD2 is a capsid-associated dynein adaptor utilized by HIV-1 for transport to the nucleus. | |
dc.format.mimetype | application/pdf | |
dc.subject | Infection | |
dc.subject | BICD2 | |
dc.subject | Nucleus | |
dc.subject | Transport | |
dc.subject | Dynein | |
dc.subject | HIV | |
dc.title | HIV-1 Engages a Dynein-Dynactin-BICD2 Complex for Infection and Transport to the Nucleus | |
dc.type | dissertation | |
dc.contributor.committeeMember | Lauren Jackson | |
dc.contributor.committeeMember | Matthew Tyska | |
dc.contributor.committeeMember | Christopher Aiken | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Microbiology and Immunology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2019-03-20 | |
local.embargo.lift | 2019-03-20 | |
dc.contributor.committeeChair | Borden Lacy | |