Jonathan Leis, PhD Professor Microbiology-Immunology Mechanism of retrovirus replication, reverse transcription, integration, proteolytic processing, and assembly Curricula: Immunology and Microbial Pathogenesis Molecular Biology and Genetics E-mail:   j-leis@northwestern.edu

Multidisciplinary molecular genetics and biochemical approaches are being used to study replication of avian and human oncogenic 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,
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.

Publications:

Brin, E. and Leis, J. HIV-1 Integrase Interaction with U3 and U5 Terminal Sequences In Vitro Defined Using Substrates with Random Sequences. J. Biol. Chem., 277: 18357-18364 (2002).

Morris, S., Johnson, M., Stavnezer, E., and Leis, J. Replication of Avian Sarcoma Virus In Vivo Requires an Interaction Between the Viral RNA and the TyC loop of the tRNATrp Primer. J. Virol. 76: 7571-7577 (2002).

VerPlank, L., Agresta, B., Grassa, T., Kikonyogo, A., Leis, J., & Carter, C. Tsg101, the prototype of a class of dominant-negative ubiquitin regulators, binds human immunodeficiency virus type 1 Pr55Gag: the L domain is a determining of binding. Proc. Natl. Acad. Sci. USA 98:7724-7729 (2001).

Kinonyogo, A., Bouamr, F., Vana, M., Xiang, Y., Aiyar, A., Carter, C., and Leis, J. Proteins Related to the Nedd4 Family of Ubiquitin Protein Ligases Interact with the L Domain of Rous Sarcoma Virus and Are Required For Gag Budding from Cells. Proc. Natl. Acad. Sci. USA. . 98: 11199-11204 (2001).