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Title page for ETD etd-03192019-104804


Type of Document Dissertation
Author Carnes, Stephanie Kaye
URN etd-03192019-104804
Title HIV-1 Engages a Dynein-Dynactin-BICD2 Complex for Infection and Transport to the Nucleus
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
Borden Lacy Committee Chair
Christopher Aiken Committee Member
Lauren Jackson Committee Member
Matthew Tyska Committee Member
Keywords
  • Infection
  • BICD2
  • Nucleus
  • Transport
  • Dynein
  • HIV
Date of Defense 2019-02-25
Availability unrestricted
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.
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