Jonathan Leis, PhD
Professor of Microbiology and Immunology
Feinberg School of Medicine
Research Interests:
Multidisciplinary molecular genetics and biochemical approaches are being used in Dr. Jonathan Leis’ lab to study replication of avian and human retroviruses. Areas of particular interest are in reverse transcription, viral DNA integration, and virion assembly.
Specific projects include studying 1) the role of viral RNA secondary structures in initiation of reverse transcription, 2) the mechanism of concerted integration of viral DNA into the host chromosome by integrase (IN) using an in vitro reconstituted system and identification of the amino acids of tIN responsible for specificity for the LTR ends, 3) the mechanism of processing of Gag and Pol polyproteins into mature viral proteins by the virus-specific protease (PR), and 4) the role of a Gag polyprotein assembly domain in budding of virus particles from cells.
In many of these studies, amino acid substitutions have been placed at biochemically or structurally important residues and the effect these changes have on viral replication and on the properties of the mutant proteins have been defined.
The first structure of a retroviral enzyme, the structure of Rous sarcoma virus protease, was solved by Leis' lab in collaboration with Dr. Wlodawer's lab in NIH.
Selected Publications:
Vana, M. L., Tang, Y., Chen, A., Medina, G., Carter, C. and Leis, J. (2004). Role of Nedd4 and ubiquitination of Rous sarcoma virus Gag in budding of virus-like particles from cells. J Virol 78, 13943-53.
Chen, A., Weber, I. T., Harrison, R. W. and Leis, J. (2006). Identification of amino acids in HIV-1 and avian sarcoma virus integrase subsites required for specific recognition of the long terminal repeat Ends. J Biol Chem 281, 4173-82.
Medina, G., Pincetic, A., Ehrlich, L. S., Zhang, Y., Tang, Y., Leis, J. and Carter, C. A. (2008). Tsg101 can replace Nedd4 function in ASV Gag release but not membrane targeting. Virology 377, 30-8.
Pincetic, A., Medina, G., Carter, C. and Leis, J. (2008). Avian sarcoma virus and human immunodeficiency virus, type 1 use different subsets of ESCRT proteins to facilitate the budding process. J Biol Chem 283, 29822-30.
Dolan, J., Chen, A., Weber, I. T., Harrison, R. W. and Leis, J. (2009). Defining the DNA substrate binding sites on HIV-1 integrase. J Mol Biol 385, 568-79.
