Dorr, Casey R.2011-05-162011-05-162011-02https://hdl.handle.net/11299/104516University of Minnesota Ph.D. dissertation. February 2011. Major: Molecular, Cellular, Developmental Biology and Genetics. Advisor: Louis Mansky. 1 computer file (PDF); vi, 103 pages, appendices A-B.Human Immunodeficiency Virus type-1 (HIV-1) replication is introduced in Chapter 1 with an emphasis on the late phase of viral replication. Literature about the production of infectious HIV-1 is reviewed in Chapter 1 while focusing on targets for suppressive HIV-1 therapy. Chapter 2 describes the discovery of triterpene compounds derived from birch trees that inhibit HIV-1 replication reformatted from Bioorganic and Medicinal Chemistry Letters. Chapter 3 investigates the anti-HIV-1 mechanisms of the triterpenes described in Chapter 2. Virus release assays conclude that the triterpene compounds target and prevents cleavage of the HIV-1 Gag product CA-SP1. Virus release assays and transmission electron microscopy indicate that the triterpene compounds SY33 and Bevirimat have a secondary mechanism of action by causing 55 kDa Gag to accumulate in cells. The Gag accumulation in cells was observed in both wild-type HIV-1 and the mutant SP1-A1V. The SP1-A1V mutant causes a decrease in susceptibility, by viral replication and CA-SP1 processing, to SY33 and Bevirimat. An Epilogue describes recommended future experiments. Appendix A describes genotypic results of an experiment to select for HIV-1 resistant to SY33 and Bevirimat using wild type and SP1-A1V as the founder viruses. The data in Appendix A suggest SP1-A1V causes reduced susceptibility to SY33 and Bevirimat. Appendix B describes the initial discovery of fatty acid derivatives with anti-HIV-1 activity.en-USBevirimatGagMaturationRetrovirusTriterpeneMolecular, Cellular, Developmental Biology and GeneticsThesis or Dissertation