Louis M. Mansky, PhD

Director, Institute for Molecular Virology

Louis M. Mansky

Contact Info

mansky@umn.edu

Office Phone 612-626-5525

Fax 612-626-5515

Lab Phone 612-624-5172

Office Address:
Institute for Molecular Virology
Room 18-256B Moos Tower
515 Delaware St S E
Minneapolis, MN 55455

Mailing Address:
Institute for Molecular Virology
18-242 Moos Tower
515 Delaware St SE
Minneapolis, MN 55455

PhD, Iowa State University

BS, Purdue University

Postdoctoral Research, Laboratory of Howard M. Temin at the University of Wisconsin, Madison

Summary

Expertise

Human cancer virology; AIDS research; human retroviruses; virus mutagenesis and evolution; virus particle assembly; antiviral drug target identification; integrative virology

Awards & Recognition

  • American Cancer Society Heroes of Hope Award

Research

Research Summary/Interests

Viral oncology; AIDS research; human retroviruses; virus evolution; virus particle assembly; antiviral drug target identification; integrative virology.

To the casual observer, Virology is typically viewed as a narrow sub-discipline in the field of Microbiology. In reality, Virology is an integrated and highly interdisciplinary discipline that has had a profound impact on our understanding of the biological and physical sciences, engineering, agriculture, and the health sciences. For example, some of the most transformative advancements in improving human health have come from basic science investigations of viruses for the development of intervention strategies – e.g., antiviral drugs and vaccines – to help treat, prevent and eradicate devastating diseases. Current understanding of the molecular genetic basis of diseases such as cancer is predicated on investigations of cancer-causing viruses. The foundations of modern molecular biology and genetics are based upon studies conducted with bacterial viruses, and continue to provide critical clues to foundational knowledge of molecular and cellular processes. Viruses have been used as tools to better understand biological systems and have been exploited time and time again as delivery systems for various types of ‘cargoes’ into cells and whole organisms.

Our research group is heavily invested in harnessing state-of-the-art technologies (both experimental and computational) in advancing the key research questions, including a fundamental understanding of 1) viral mutagenesis and evolution (and therapeutic implications), 2) molecular and cellular aspects of virus particle assembly (and therapeutic implications). We primarily study the human retroviruses – human T-cell leukemia virus (HTLV; cause of an adult T-cell leukemia) and human immunodeficiency virus (HIV; cause of AIDS). We also conduct comparative studies with a variety of other viruses. Key interdisciplinary technologies we are currently employing span from quantitative imaging techniques (e.g., fluorescence microscopy at single molecule resolution, cryo-transmission electron tomography) to ultrasensitive, next-generation DNA sequencing (e.g., single-strand consensus sequencing) to large data informatics analyses (sensitive mutation detection bioinformatics analyses, 3D-reconstructions of virus particle structure).

Our research group is strongly committed to the career development of predoctoral and postdoctoral students, in order to prepare them for careers in today’s workplace, which can lead in a whole variety of directions, including the directing of their own research programs. Our research group takes full advantage of the activities offered by the Institute for Molecular Virology and NIH-supported Institute for Molecular Virology Training Program.

Publications from our research group can be found in PubMed.

Research Funding Grants

  • Fogarty KH, Berk S, Grigsby IF, Chen Y, Mansky LM, Mueller JD. 2013. Interrelationship between cytoplasmic retroviral Gag concentration and Gag-membrane association. Journal of Molecular Biology. Epub ahead of print.
  • Tabah AA, Tardif K, Mansky LM. 2013. Anti-HIV-1 Activity of Trim 37. Journal of General Virology. Epub ahead of print.
  • Sun M, Grigsby IF, Gorelick RJ, Mansky LM, Musier-Forsyth K. 2013. Retrovirus-specific differences in matrix and nucleocapsid protein-nucleic acid interactions: implications for genomic RNA packaging. Journal of Virology. Epub ahead of print.
  • Dapp MJ, Bonnac, L, Patterson, SE, Mansky, LM. 2013. Discovery of novel ribonucleoside analogs with activity against human immunodeficiency virus type 1. Journal of Virology. Epub ahead of print.
  • Clouser, CL, Bonnac, L, Mansky, LM, Patterson, SE. 2013. Characterization of permeability, stability, and anti-HIV-1 activity of decitabine and gemcitabine divalerate prodrugs. Antiviral Chemistry & Chemotherapy. Epub ahead of print.
  • Rawson, JM, Heineman, RH, Beach, LB, Martin, JL, Schnettler, EK, Dapp, MJ, Patterson, SE, Mansky, LM. 2013. 5,6-Dihydro-5-aza-2'-deoxycytidine potentiates the anti-HIV-1 activity of ribonucleotide reductase inhibitors.Bioorg Med Chem. Nov 15;21(22):7222-8.
  • Bonnac, LF, Mansky, LM, Patterson, SE. 2013. Structure-activity relationships and design of viral mutagens and application to lethal mutagenesis. Journal of Medicinal Chemistry. Epub ahead of print
  • Holtz CM, Sadler HA and Mansky LM. 2013. APOBEC3G cytosine deamination hotspots are defined by both sequence context and single-stranded DNA secondary structure. Nucleic Acids Research 41:6139-6148.
  • Holtz CM, Mansky LM. 2013. Variation of HIV-1 mutation spectra among cell types. J Virol. Epub ahead of print
  • Dapp MJ, Patterson, SE, Mansky, LM. 2012. Back to the future: revisiting HIV-1 lethal mutagenesis. Trends in Microbiology. 21:56-62.
  • Dapp MJ, Heineman, RH, Mansky LM. 2012. Interrelationship between HIV-1 fitness and mutation rate. J Mol Biol. 425:41-53.
  • Clouser, CL, Chauhan, J, Bess, MA, Oploo, JL, Zhou, D, Dimick-Gray, S, Mansky, LM, Patterson, SE. 2012. Anti-HIV-1 activity of resveratrol derivatives and synergistic inhibition of HIV-1 by the combination of resveratrol and decitabine. Bioorg Med Chem Lett. 22:6642-6646.
  • Dapp MJ, Holtz CM, Mansky LM. 2012. Concomitant lethal mutagenesis of human immunodeficiency virus type 1. J Mol Biol. 419:158-170.
  • Clouser CL, Holtz CM, Mullet M, Crankshaw DL, Briggs JE, O’Sullivan MG, Patterson SE, Mansky LM. 2012. Activity of a novel combined antiretroviral therapy of gemcitabine and decitabine in a mouse model for HIV-1. Antimicrobial Agents and Chemotherapy. 56:1942-1948.
  • Greggs, WM 3rd, Clouser CL, Patterson SE, Mansky LM. 2012. Discovery of drugs that possess activity against feline leukemia virus. Journal of General Virology 93:900-905.
  • Guenzel CA, Hérate C, Le Rouzic E, Maidou-Peindara P, Sadler HA, Rouyez MC, Mansky LM, Benichou S. 2012. Recruitment of the nuclear form of uracil DNA glycosylase into virus particles participates in the full infectivity of HIV-1. J Virol. 86:2533-44.
  • Wu K, Chen L, Peng G, Zhou W, Pennell CA, Mansky LM, Geraghty RJ, Li F. 2011. A virus-binding hot spot on human angiotensin-converting enzyme 2 is critical for binding of two different coronaviruses J Virol. 2011 85:5331-7.
  • Fogarty, KH, Zhang, W, Grigsby, IF, Johnson, J, Chen, Y, Mueller, JD and LM Mansky. 2011. New insights into HTLV-1 particle structure, assembly and Gag-Gag interactions in living cells. Viruses 3(6):770-93.
  • Fogarty, K.H., Johnson, J.L., Grigsby, I.F., MacDonald, P.J., Smith, E.M., Chen, Y., Rawson, J.M., Mansky, L.M., and J.D. Mueller. 2011. Characterization of cytoplasmic Gag-Gag interactions by dual-color z-scan fluorescence fluctuation spectroscopy. Biophysical Journal 100:1587-1595.
  • Greggs, W.M., Clouser, C.L., Patterson, S.E., and L.M. Mansky. 2011. Broadening the use of antiretroviral therapy: the case for feline leukemia virus. Therapeutics and Clinical Risk Management 7:115 – 122.
  • Clouser, C.L., Holtz, C.M., Mullet, M., Crankshaw, D.L., Briggs, J.E., Chauhan, J., Patterson, S.E., and L.M. Mansky. 2011. Analysis of the ex vivo and in vivo antiretroviral activity of gemcitabine. PLoS One 6:e15840
  • Ni, Z., Knorr, D.A., Clouser, C.L., Hexum, M.K., Souther, P., Mansky, L.M., Park, I.-H., and D.S. Kaufman. 2011. Human pluripotent stem cells produce natural killer cells that mediate anti-HIV-1 activity utilizing diverse cellular mechanisms. Journal of Virology 85:43-50

Publications

  • Beach LB, Rawson JM, Kim B, Patterson SE, Mansky LM. 2014. Novel inhibitors of human immunodeficiency virus type 2 infectivity. Journal of General Virology. Epub ahead of print.
  • Maldonado JO, Martin JL, Mueller JD, Zhang W, Mansky LM. 2014. New insights into retroviral Gag-Gag and Gag-membrane interactions. Frontiers in Microbiology. 5:302. doi: 10.3389/fmicb.2014.00302. eCollection 2014.
  • Tabah AA, Tardif K, Mansky LM. 2014. Anti-HIV-1 activity of Trim 37. Journal of General Virology. 94:960-967.
  • Fogarty KH, Berk S, Grigsby IF, Chen Y, Mansky LM, Mueller JD. 2014. Interrelationship between cytoplasmic retroviral Gag concentration and Gag-membrane association. Journal of Molecular Biology. 426(7):1611-24.
  • Sun M, Grigsby IF, Gorelick RJ, Mansky LM, Musier-Forsyth K. 2014. Retrovirus-specific differences in matrix and nucleocapsid protein-nucleic acid interactions: implications for genomic RNA packaging. Journal of Virology. 88(2):1271-80.
  • Dapp MJ, Bonnac, L, Patterson, SE, Mansky, LM. 2014. Discovery of novel ribonucleoside analogs with activity against human immunodeficiency virus type 1. Journal of Virology.88(1):354-63.
  • Clouser, CL, Bonnac, L, Mansky, LM, Patterson, SE. 2013. Characterization of permeability, stability, and anti-HIV-1 activity of decitabine and gemcitabine divalerate prodrugs. Antiviral Chemistry & Chemotherapy. Aug 30. doi: 10.3851/IMP2682. Epub ahead of print.
  • Rawson, JM, Heineman, RH, Beach, LB, Martin, JL, Schnettler, EK, Dapp, MJ, Patterson, SE, Mansky, LM. 2013. 5,6-Dihydro-5-aza-2'-deoxycytidine potentiates the anti-HIV-1 activity of ribonucleotide reductase inhibitors. Bioorganic and Medicinal Chemistry. 21:7222-7228.
  • Bonnac, LF, Mansky, LM, Patterson, SE. 2013. Structure-activity relationships and design of viral mutagens and application to lethal mutagenesis. J. Med. Chem. 56:9403-9414.
  • Holtz CM, Sadler, HA, Mansky, LM. 2013. APOBEC3G cytosine deamination hotspots are defined by both sequence context and single-stranded DNA secondary structure. Nucleic Acids Research 41:6139-6148.
  • Holtz CM, Mansky LM. 2013. Variation of HIV-1 mutation spectra among cell types. J Virol. 87:5296-5299.
  • Dapp MJ, Patterson, SE, Mansky, LM. 2012. Back to the future: revisiting HIV-1 lethal mutagenesis. Trends in Microbiology. 21:56-62.
  • Dapp MJ, Heineman, RH, Mansky LM. 2012. Interrelationship between HIV-1 fitness and mutation rate. J Mol Biol. 425:41-53.
  • Clouser, CL, Chauhan, J, Bess, MA, Oploo, JL, Zhou, D, Dimick-Gray, S, Mansky, LM, Patterson, SE. 2012. Anti-HIV-1 activity of resveratrol derivatives and synergistic inhibition of HIV-1 by the combination of resveratrol and decitabine. Bioorg Med Chem Lett. 22:6642-6646.
  • Dapp, MJ, Holtz, CM, Mansky LM. 2012. Concomitant lethal mutagenesis of human immunodeficiency virus type 1. J Mol Biol. 419:158-170.
  • Clouser CL, Holtz CM, Mullet M, Crankshaw DL, Briggs JE, O’Sullivan MG, Patterson SE, Mansky LM. 2012. Activity of a novel combined antiretroviral therapy of gemcitabine and decitabine in a mouse model for HIV-1. Antimicrobial Agents and Chemotherapy. 56:1942-1948.
  • Greggs, WM 3rd, Clouser CL, Patterson SE, Mansky LM. 2012. Discovery of drugs that possess activity against feline leukemia virus. Journal of General Virology 93:900-905.
  • Guenzel CA, Hérate C, Le Rouzic E, Maidou-Peindara P, Sadler HA, Rouyez MC, Mansky LM, Benichou S. 2012. Recruitment of the nuclear form of uracil DNA glycosylase into virus particles participates in the full infectivity of HIV-1. J Virol. 86:2533-44.
  • Fogarty, K.H., Zhang, W., Grigby, I.F., Johnson, J.L., Chen, Y., Mueller, J.D., and L.M. Mansky. 2011. New insights into HTLV-1 particle structure, assembly and Gag-Gag interactions in living cells. Viruses 3:770-793.
  • Wu K, Chen L, Peng G, Zhou W, Pennell CA, Mansky LM, Geraghty RJ, Li F. 2011. A virus-binding hot spot on human angiotensin-converting enzyme 2 is critical for binding of two different coronaviruses J Virol. 2011 85:5331-7.
  • Fogarty, K.H., Johnson, J.L., Grigsby, I.F., MacDonald, P.J., Smith, E.M., Chen, Y., Rawson, J.M., Mansky, L.M., and J.D. Mueller, J.D. 2011. Characterization of cytoplasmic Gag-Gag interactions by dual-color z-scan fluorescence fluctuation spectroscopy. Biophysical Journal. 100:1587-95.
  • Greggs WM 3rd, Clouser CL, Patterson SE, Mansky LM. 2011. Broadening the use of antiretroviral therapy: the case for feline leukemia virus. Therapeutics and Clinical Risk Management. 7:115-22.
  • Clouser, C.L., Holtz, C.M., Mullet, M., Crankshaw, D.L., Briggs, J.E., Chauhan, J., VanHoutan, I.M., Patterson, S.E., and L.M. Mansky. 2011. Analysis of the ex vivo and in vivo antiretroviral activity of gemcitabine. PLoS One 6:e15840
  • Ni, Z., Knorr, D.A., Clouser, C.L., Hexum, M.K., Southern, P., Mansky, L.M., Park, I.-H., and D.S. Kaufman. 2011. Human pluripotent stem cells produce natural killer cells that mediate anti-HIV-1 activity utilizing diverse cellular mechanisms. Journal of Virology 85:43-50.
  • Dorr, C.R., Yemets, S., Kokomitsyna, O., Krasutsky, P., and L.M. Mansky. 2011. Triterpene derivatives that inhibit human immunodeficiency virus type 1 replication. Bioorganic and Medicinal Chemistry Letters 21:542-545.
  • Grigsby, I.F., Zhang, W., Johnson, J.L., Fogarty, K.H., Chen, Y., Rawson, J.M., Crosby, A.J., Mueller, J.D., and L.M. Mansky. 2010. Biophysical analysis of HTLV-1 particles reveals novel insights into particle morphology and Gag stochiometry. Retrovirology 7:75
  • Sanjuan, R., Nebot, M.R., Chirico, N., Mansky, L.M., and R. Belshaw. Viral mutation rates. Journal of Virology. 84:9733-9748.
  • Clouser, C.L., Patterson, S.E., and L.M. Mansky. 2010. Exploiting drug repositioning for the discovery of a novel HIV combination therapy. Journal of Virology 84:9301-9309.
  • Sadler, H.A., Stenglein, M.D., Harris, R.S., and L.M. Mansky. 2010. APOBEC3G contributes to HIV-1 variation through sublethal mutagenesis. Jounral of Virology 84:7396-7404.
  • Grigsby, I.F., Pham, L., Mansky, L.M., Gopalakrishnan, R., Carlson, A. and K.C. Mansky, K.C. 2010. Tenofovir treatment of primary osteoblasts alters gene expression profiles: implications for bone mineral density loss. Biochemical and Biophysical Research Communications 394:48-53.
  • Grigsby, I.F., Pham, L., Gopalakrishnan, R., Mansky, L.M., and K.C. Mansky. 2010. Downregulation of Gnas, Got2 and Snord32a following tenofovir exposure of primary osteoclasts. Biochemical and Biophysical Research Communications 391:1324-1329.
  • Grigsby, I.F., Pham, L., Mansky, L.M., Gopalakrishnan, R., and K.C. Mansky. 2009. Tenofovir-associated bone density loss. Therapeutics and Clinical Risk Management 6:41-47.
  • Dapp, M.D., Clouser, C.L., Patterson, S.E. and L.M. Mansky. 2009. 5-Azacytidine can induce lethal mutagenesis in human immunodeficiency virus type 1. Journal of Virology 83:11950-58.
  • Chen, Y. Wu, B., Musier-Forsyth, K., Mansky, L.M., and J.D. Mueller. 2009. Fluorescence fluctuation spectroscopy on viral-like particles reveals variable Gag stoichiometry. Biophysics Journal 96:1961:1969.
  • Nishiguichi, M.K., Hirsch, A.M., deVinney, R., Vendantam, G., Riley, M.A., and L.M. Mansky. 2008. Deciphering evolutionary mechanisms between mutualistic and pathogenic symbioses. Life and Environment 58: 87-106.
  • 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.
  • Jewell, N.A. and L.M. Mansky. 2005. Packaging of heterologous RNAs by a minimal bovine leukemia virus RNA packaging signal into virus particles. 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.
  • 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.
  • 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.
  • 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.
  • 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.