The release of retrovirus particles from the infected cell is greatly stimulated by """"""""late"""""""" domains present within the Gag precursor protein. Three distinct retroviral late-domain sequences have been identified: Pro-Thr/Ser-Ala-Pro (PTAP or PSAP), Pro-Pro-X-Tyr (PPXY, where X is any amino acid), and Tyr-Pro-Xn-Leu (YPXnL). We played a key early role in identifying the PTAP late domain of HIV-1, and, along with other labs, contributed to the discovery that late domains function by interacting with components of the endosomal sorting complex required for transport (ESCRT) machinery. We continue to be actively involved in elucidating the host cell machinery required for the release of HIV-1 and other lentiviruses (e.g., EIAV and FIV) and are in the process of identifying inhibitors of retrovirus budding. Much of our recent effort in this area is focused on the role of Alix in HIV-1 budding and cell-cell transfer. [Corresponds to Freed Project 2 in the October 2011 site visit report of the HIV Drug Resistance Program]

National Institute of Health (NIH)
National Cancer Institute (NCI)
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Cancer Institute Division of Basic Sciences
Zip Code
Tedbury, Philip R; Freed, Eric O (2015) HIV-1 gag: an emerging target for antiretroviral therapy. Curr Top Microbiol Immunol 389:171-201
Park, Sang Yoon; Waheed, Abdul A; Zhang, Zai-Rong et al. (2014) HIV-1 Vpu accessory protein induces caspase-mediated cleavage of IRF3 transcription factor. J Biol Chem 289:35102-10
Bird, Sara W; Kirkegaard, Karla; Agbandje-McKenna, Mavis et al. (2014) The ins and outs of viral infection: keystone meeting review. Viruses 6:3652-62
Waheed, Abdul A; Kuruppu, Nishani D; Felton, Kathryn L et al. (2014) In COS cells Vpu can both stabilize tetherin expression and counteract its antiviral activity. PLoS One 9:e111628
Li, Minghua; Ablan, Sherimay D; Miao, Chunhui et al. (2014) TIM-family proteins inhibit HIV-1 release. Proc Natl Acad Sci U S A 111:E3699-707
Keren-Kaplan, Tal; Attali, Ilan; Estrin, Michael et al. (2013) Structure-based in silico identification of ubiquitin-binding domains provides insights into the ALIX-V:ubiquitin complex and retrovirus budding. EMBO J 32:538-51
Waheed, Abdul A; Freed, Eric O (2012) HIV type 1 Gag as a target for antiviral therapy. AIDS Res Hum Retroviruses 28:54-75
Kuo, Lillian; Freed, Eric O (2012) ARRDC1 as a mediator of microvesicle budding. Proc Natl Acad Sci U S A 109:4025-6
Kim, Sung-Eun; Liu, Fa; Im, Young Jun et al. (2011) Elucidation of New Binding Interactions with the Tumor Susceptibility Gene 101 (Tsg101) Protein Using Modified HIV-1 Gag-p6 Derived Peptide Ligands. ACS Med Chem Lett 2:337-341
Im, Young Jun; Kuo, Lillian; Ren, Xuefeng et al. (2010) Crystallographic and functional analysis of the ESCRT-I /HIV-1 Gag PTAP interaction. Structure 18:1536-47

Showing the most recent 10 out of 18 publications