Louis M. Mansky, Ph.D. Professor Departments of Microbiology and Diagnostic and Biological Sciences Institute for Molecular Virology Iowa State University, 1990, Ph.D. mansky@umn.edu 612-626-5525 office 612-624-0667 lab

Research Interests:

Cell and molecular biology of HIV and HTLV; Antiviral drug discovery and development; Antiviral drug resistance; HIV genetic variation, evolution and population genetics; Viral quasispecies; Virus assembly; Evolution of emerging viruses

The study of retroviruses over the past three decades has led to some of the most important discoveries in biomedical research, and has laid the foundation for biotechnology, cancer research, AIDS research, and human gene therapy. The discovery of reverse transcriptase helped to create the biotechnology industry, the discovery of oncogenes helped to advance our understanding of the genetic basis of cancer, and the discovery of retroviruses in higher animals led to the discovery of human retroviruses that cause cancer (HTLV-1) and AIDS (HIV-1). The creation of retroviral
vectors and retrovirus helper cell lines helped to establish the field of gene therapy.

Retroviruses are relatively simple viruses that encode from three to ten genes, but are unusual in that they undergo a step in their life cycle called reverse transcription, which is the synthesis of double-stranded DNA from single-stranded RNA. We are exploring the accuracy of this process in
HIV-1 replication and how it influences not only the evolution of HIV-1 variants that are resistant to anti-HIV-1 drugs, but also how it influences the development of an effective AIDS vaccine. We are also exploring how the APOBEC3 proteins impact HIV evolution and drug resistance. A long-term goal of our efforts is to define the molecular determinants for HIV-1 mutation in order to 1) manipulate HIV-1 evolution and improve the efficacy of anti-HIV-1 drugs, and 2) provide the basis for new intervention strategies.

Central steps in the retrovirus life cycle include the recognition of the genomic RNA by viral protein and virus particle assembly. The details behind how particle assembly occurs and subsequent virus transmission is currently being investigated. We are helping to apply the novel biophysical technology of flourescence fluctuation spectroscopy (FFS) to study retrovirus assembly. A long term goal of these studies is better understand the detailed steps of virus assembly. Such information should identify new targets for the rational design of antiviral drugs.

Institute for Molecular Virology

The Mansky Lab

Selected Recent Publications:

• Mbisa J.L., Barr R., Thomas J.A., Vandegraaff N., Dorweiler I.J., Svarovskaia E.S., Brown W.L., Mansky L.M., Gorelick R.J., Harris R.S., Engelman A., Pathak V.K. 2007. Human immunodeficiency virus type 1 cDNAs produced in the presence of APOBEC3G exhibit defects in plus-strand DNA transfer and integration. Journal of Virology 81:7099-7110.

• Hache G., Mansky L.M., and Harris R.S. 2006. Human APOBEC3 proteins, retrovirus restriction, and HIV drug resistance. AIDS Rev. 8:148-57.

• Dorweiler, I.J., Ruone, S.J., Wang, H., Burry, R.W., and L.M. Mansky. 2006. Role of the human T-cell leukemia virus type 1 PTAP motif in Gag targeting and particle release. Journal of Virology 80:3634-3643.

• Chen, R., Yokohama M., Sato H., Reilly C. Mansky, LM. 2005. Human immunodeficiency virus mutagenesis during antiviral therapy: impact of drug-resistant reverse transcriptase and nucleoside and nonnucleoside reverse transcriptase inhibitors on human immunodeficiency virus type 1 mutation frequencies. Journal of Virology 79:12045-57. Abstract

• Jewell, N.A. and L.M. Mansky. 2005. Packaging of heterologous RNAs by a minimal bovine leukemia virus RNA packaging signal into virus particles.Construction and characterization of deltaretrovirus indicator cell lines. Archives of Virology 150:1161-73.

• Jewell, N.A. and L.M. Mansky. 2005. Construction and characterization of deltaretrovirus indicator cell lines. Journal of Virological Methods 123:17-24. Abstract

• Chen, R., Quinones-Mateu, M.E., and L.M. Mansky. 2005. HIV-1 mutagenesis during antiretroviral therapy: implications for successful drug treatment. Frontiers in Biosciences 10:743-750. Abstract

• Chen, R., Quinones-Mateu, M.E., and L.M. Mansky. 2004. Drug resistance, virus fitness and HIV-1 mutagenesis. Current Pharmaceutical Design 10:4065-4070. Abstract

• Spidel, J.L., Craven, R.C., Wilson, C.B., Patnaik, A., Wang, H., Mansky, L.M., and J.W. Wills. 2004. Lysines close to the Rous sarcoma virus late domain critical for budding. Journal of Virology 78:10606-10616.

• Chen, R., LeRouzic, E. Kearney, J.A., Mansky, L.M., and S. Benichou. 2004. Vpr-mediated incorporation of UNG2 into HIV-1 particles is required to modulate the virus mutation rate and for replication in macrophages. J. Biol. Chem. 279:28419-25.

• Weiss, K.K., Chen, R., Lee, K., Bambara, R.A., Mansky, L.M., and B. Kim. 2004. A role for dNTP binding of human immunodeficiency virus type 1 reverse transcriptase in viral mutagenesis. Biochemistry 43:4490-4500. Abstract

• Wang, H., N. M. Machesky, and L. M. Mansky. 2004. Both the PPPY and PTAP motifs in the human T-cell leukemia virus type 1 Gag protein are required for particle release. Journal of Virology 78:1503-1512.

Last modified on: November 21, 2006