We seek to understand how processive transcription of proviral HIV is achieved in latently infected CD4+ T cells, which are well established to be the major reservoir of latent and replication-competent proviruses in HIV+ individuals under life-long antiretroviral therapy. More specifically, my research focuses on studying host and viral control of the processivity transcription factor P-TEFb. This research is being carried out with the understanding that since P-TEFb kinase is absolutely required for proviral transcription, delineating its activation mechanism by cellular signal transduction and HIV Tat, and also the means by which P-TEFb mediates Tat-dependent proviral transcription elongation is of paramount importance in contributing to efforts currently aimed at eradicating latent HIV reservoirs which are resistant to antiretroviral therapy.
Mbonye U., Gokulrangan G., Datt M., Dobrowolski C., Cooper M., Chance M., Karn J. Phosphorylation of CDK9 at Ser175 enhances HIV transcription and is a marker of activated P-TEFb in CD4+ T lymphocytes. PLoS Pathogens 2013; 9(5):e1003338. [PubMed]
Mbonye U, Karn J. Control of HIV latency by epigenetic and non-epigenetic mechanisms. Curr HIV Res. (2011) Curr HIV Res, 9(8):554-67. [PubMed]
Kim YK, Mbonye U, Hokello J, Karn J. T-cell receptor signaling enhances transcriptional elongation from latent HIV proviruses by activating P-TEFb through an ERK-dependent pathway. J Mol Biol. 2011 Jul 29. Epub 2011 July 14. [PubMed]
Mbonye UR, Song I. Posttranscriptional and posttranslational determinants of cyclooxygenase expression. BMB Rep. 2009; 42(9):552-60. [PubMed]
Mbonye UR, Yuan C, Harris CE, Sidhu RS, Song I, Arakawa T, Smith WL. Two distinct pathways for cyclooxygenase-2 protein degradation. J Biol Chem. 2008; 283(13):8611-23. [PubMed]
Kang YJ, Mbonye UR, DeLong CJ, Wada M, Smith WL. Regulation of intracellular cyclooxygenase levels by gene transcription and protein degradation. Prog Lipid Res. 2007 Mar;46(2):108-25. Epub 2007 Jan 18. [PubMed]
Mbonye UR, Wada M, Rieke CJ, Tang HY, Dewitt DL, Smith WL: The 19-amino acid cassette of cyclooxygenase-2 mediates entry of the protein into the endoplasmic reticulum-associated degradation system. J Biol Chem. 2006 Nov 24;281(47):35770-8. Epub 2006 Sep 25. [PubMed]