Research Program: Genetic Mechanisms of Cancer
Director, Institute for Molecular Virology
Professor, Departments of Diagnostic and Biological Sciences and Microbiology
Member, Center for Drug Design

mansky@umn.edu
612-626-5525 — office
Preferred method of contact: e-mail

Dr. Mansky received his B.S. degree from Purdue University and his Ph.D. degree from Iowa State University. He conducted postdoctoral training in the laboratory of Dr. Howard M. Temin at the McArdle Laboratory for Cancer Research, University of Wisconsin-Madison.

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.

Selected Publications

Mbisa JL, Barr R, Thomas JA, Vandegraaff N, Dorweiler IJ, Svarovskaia ES, Brown WL, Mansky LM, Gorelick RJ, Harris RS, Engelman A, Pathak VK. Human immunodeficiency virus type 1 cDNAs produced in the presence of APOBEC3G exhibit defects in plus-strand DNA transfer and integration. J Virol. 2007;81:7099-7110.

Hache G, Mansky LM, Harris RS. Human APOBEC3 proteins, retrovirus restriction, and HIV drug resistance. AIDS Rev. 2006;8:148-57.

Dorweiler IJ, Ruone SJ, Wang H, Burry RW, Mansky LM. Role of the human T-cell leukemia virus type 1 PTAP motif in Gag targeting and particle release. J Virol. 2006;80:3634-3643.

Chen R, Yokohama M, Sato H, Reilly C, Mansky LM. Human mmunodeficiency virus mutagenesis during antiviral therapy: impact of rug-resistant reverse transcriptase and nucleoside and nonnucleoside everse ranscriptase inhibitors on human immunodeficiency virus type 1 utation requencies, J Virol. 2005;79:12045-57.

Jewell NA, Mansky LM. Packaging of heterologous RNAs by a inimal bovine leukemia virus RNA packaging signal into virus particles. Arch Virol 2005;150:1161-73.

Jewell NA, Mansky LM. Construction and characterization of eltaretrovirus indicator cell lines. J Virol Methods 2005;23:17-24.

Chen R, Quinones-Mateu ME, Mansky LM. HIV-1 mutagenesis during antiretroviral therapy: implications for successful drug treatment. Front Biosci. 2005;10:743-50.