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Title page for ETD etd-03302009-150129

Type of Document Dissertation
Author Rold, Christopher James
URN etd-03302009-150129
Title The role of the cellular proteasome and ubiquitin in post-entry restriction of retroviruses by TRIM5α
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
Dr. Terence S. Dermody Committee Chair
Dr. Brian Wadzinski Committee Member
Dr. Christopher Aiken Committee Member
Dr. Richard T. D'Aquila Committee Member
Dr. Todd R. Graham Committee Member
  • post-entry restriction
  • TRIM5á
  • HIV-1
  • retrovirus
Date of Defense 2009-03-09
Availability unrestricted
The host protein TRIM5α inhibits retroviral infection at an early post-penetration stage by binding to the incoming viral capsid. Interaction with TRIM5α results in a failure of the virus to complete reverse transcription through an unknown mechanism. I have discovered that infection of cells with a restricted retrovirus leads to degradation of TRIM5α in the target cells. This degradation strongly correlates with restriction, is dose dependent, and inversely correlates with infection. Viral-induced degradation of TRIM5α is dependent on the presence of the RING domain of TRIM5α and a functional cellular proteasome. I have also found evidence linking the UbcH5 family of E2 ubiquitin conjugases to a role in post-entry restriction of HIV-1 by rhesus macaque-derived TRIM5α. These findings establish a connection between post-entry restriction by TRIM5α and the ubiquitin-proteasome pathway and indicate a mechanism of retroviral restriction by TRIM5α.
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