Research Summary

Research in the Levy laboratory is directed at understanding the interaction of viruses and the immune system in microbial pathogenesis. It focuses on HIV infection with the goal of designing novel antiviral therapies and an effective AIDS vaccine for which both innate and adaptive responses are needed. Biologic, serologic, and molecular characterization of several HIV-1 and HIV-2 strains has revealed their extensive heterogeneity and how viruses can evolve differently in the same individual in the immune system, bowel, and the brain. A major emphasis in the laboratory has been on anti-HIV innate immune responses. The research group is evaluating the role of plasmacytoid dendritic cells (PDC), the main producers of type 1 interferons. Studies are directed at understanding how HIV-infected cells induce interferon production from PDC and what cell surface molecules, including toll-like receptors (TLR), are involved in this process. An important potent innate response we have discovered is the ability of CD8+ lymphocytes to suppress HIV replication without killing the cells. This novel CD8+ cell noncytotoxic antiviral response (CNAR) is mediated by an as yet unidentified, natural CD8+ cell antiviral factor (CAF) that blocks HIV transcription. In summary, the Levy laboratory has been conducting studies to identify CAF through RNA Seq procedures, to determine the best strategy for an AIDS vaccine and to use genetically modified stem cell approaches towards a potential HIV cure.

Research Funding

  • March 6, 2017 - February 28, 2020 - Characterization of a New Anti-HIV Immune Protein , Principal Investigator . Sponsor: NIH/NIAID, Sponsor Award ID: R21AI129685
  • May 1, 2014 - April 30, 2018 - HIV Cure with CCr5 (-) Human IPS Hematopoietic Stem Cells , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI102825
  • March 1, 1982 - May 31, 2015 - Bio-Organic Biomedical Mass Spectrometry Resource , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P41RR001614
  • June 7, 2012 - August 31, 2013 - HIV cure with CCR5 (-) human IPS hematopoietic stem cells , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R56AI102825
  • July 1, 2010 - June 30, 2013 - Protection from HIV Infection in Intravenous Drug Users , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21DA030272
  • July 1, 2003 - February 28, 2012 - Role of Innate Immunity in Controlling HIV Infection , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI056992
  • September 30, 2004 - June 30, 2010 - MBSR, Stress Arousal and Immune Response in Early HIV , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P01AT002024
  • July 1, 2003 - August 31, 2008 - Role of Innate Immunity in Controlling HIV Infection , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R56AI056992
  • July 1, 1997 - June 30, 2008 - Immunologic &Virologic Features of Early HIV Infection , Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01AI041531
  • August 1, 1990 - January 31, 2007 - UCSF AIDS RESEARCH TRAINING PROGRAM , Principal Investigator . Sponsor: NIH, Sponsor Award ID: T32AI007395
  • March 1, 2003 - February 29, 2004 - 20Years of HIV Research: From Discovery to Understanding , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R13AI054154
  • June 1, 1999 - November 30, 2002 - ANIMAL MODEL FOR HIV VACCINE DEVELOPMENT , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01RR014181
  • April 1, 2001 - March 31, 2002 - Suppression of HIV replication by CD8+ cells , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21AI049926
  • June 1, 1990 - September 29, 2001 - SUPPRESSION OF HIV REPLICATION BY CD8+ CELLS , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21AI030350
  • September 30, 1995 - September 29, 2000 - VERTICAL TRANSMISSION OF HIV-1 IN THAILAND--VIRAL FACTOR , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R03TW000535
  • June 1, 1990 - June 30, 2000 - SUPPRESSION OF HIV REPLICATION BY CD8+ CELLS , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI030350
  • August 1, 1994 - July 31, 1998 - HIV 2 INFECTION--A POTENTIAL MODEL , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI034704
  • September 30, 1993 - June 30, 1997 - SIV/HIV CHIMERAS--AN ANIMAL MODEL FOR HIV INFECTION , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI034742
  • April 1, 1994 - March 31, 1997 - VIROLOGY AND IMMUNOLOGY OF CHRONIC FATIGUE SYNDROME , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI035572
  • September 30, 1989 - July 31, 1993 - ENHANCING ANTIBODIES IN HIV INFECTION , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI029394
  • April 1, 1987 - March 31, 1990 - AIDS RETROVIRUS FEATURES AFFECTING ANTIVIRAL THERAPY , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI024499

Education

Wesleyan University, Middletown, CT, BA, 1960, Biology
Universite de Paris, France, 1961, Regeneration
Columbia University, New York, MD, 1965, Medicine and Virology

Honors & Awards

  • UCSF 150th Anniversary Alumni Award, University of California, San Francisco, 2015
  • Gold Medal for Excellence in Medical Research, Columbia University, 2008
  • Fellow, American Academy of Arts and Sciences, 2004
  • Fellow, American Academy of Microbiology, 2003
  • UCSF 45th Faculty Research Lecturer, University of California, San Francisco, 2002
  • Doctor of Science Honorary Degree, Wesleyan University, 1996
  • Fellow, American Association for the Advancement of Science, 1993

Selected Publications

  1. Stewart O, Gruber C, Randolph HE, Patel R, Ramba M, Calzoni E, Huang LH, Levy J, Buta S, Lee A, Sazeides C, Prue Z, Hoytema van Konijnenburg DP, Chinn IK, Pedroza LA, Lupski JR, Schmitt EG, Cooper MA, Puel A, Peng X, Boisson-Dupuis S, Bustamante J, Okada S, Martin-Fernandez M, Orange JS, Casanova JL, Milner JD, Bogunovic D Monoallelic expression can govern penetrance of inborn errors of immunity.  View on PubMed
  2. Morvan MG, Teque F, Ye L, Moreno ME, Wang J, VandenBerg S, Stoddart CA, Kan YW, Levy JA. Genetically edited CD34+ cells derived from human iPS cells in vivo but not in vitro engraft and differentiate into HIV-resistant cells. Proc Natl Acad Sci U S A. 2021 05 18; 118(20).  View on PubMed
  3. Morvan MG, Teque FC, Locher CP, Levy JA. The CD8+ T Cell Noncytotoxic Antiviral Responses. Microbiol Mol Biol Rev. 2021 05 19; 85(2).  View on PubMed
  4. Levy JA, Coutinho RA, Saag MS. AIDS new editor announcement. AIDS. 2020 11 15; 34(14):1995.  View on PubMed
  5. Levy JA. The need to reassess our approaches at HIV cure and prevention. AIDS. 2020 11 15; 34(14):2141-2143.  View on PubMed
  6. Ye L, Wang J, Teque F, Xie F, Tan Y, Kan YW, Levy JA. Generation of HIV-1-infected patients' gene-edited induced pluripotent stem cells using feeder-free culture conditions. AIDS. 2020 07 01; 34(8):1127-1139.  View on PubMed
  7. Teque F, Ye L, Xie F, Wang J, Morvan MG, Kan YW, Levy JA. Genetically-edited induced pluripotent stem cells derived from HIV-1-infected patients on therapy can give rise to immune cells resistant to HIV-1 infection. AIDS. 2020 07 01; 34(8):1141-1149.  View on PubMed
  8. Hecht FM, Moskowitz JT, Moran P, Epel ES, Bacchetti P, Acree M, Kemeny ME, Mendes WB, Duncan LG, Weng H, Levy JA, Deeks SG, Folkman S. A randomized, controlled trial of mindfulness-based stress reduction in HIV infection. Brain Behav Immun. 2018 10; 73:331-339.  View on PubMed
  9. Levy JA, Murphy EL. Schwab M (ed.) Encyclopedia of Cancer. Human T-Lymphotropic Virus. 2017; 3:2146 - 2149.  View on PubMed
  10. Blazek D, Teque F, Mackewicz C, Peterlin M, Levy JA. The CD8+ cell non-cytotoxic antiviral response affects RNA polymerase II-mediated human immunodeficiency virus transcription in infected CD4+ cells. J Gen Virol. 2016 Jan; 97(1):220-224.  View on PubMed
  11. Levy JA. Discovery of another anti-HIV protein in the search for the CD8+ cell anti-HIV Factor. Proc Natl Acad Sci U S A. 2015 Jun 30; 112(26):7888-9.  View on PubMed
  12. Levy JA. Dispelling myths and focusing on notable concepts in HIV pathogenesis. Trends Mol Med. 2015 Jun; 21(6):341-53.  View on PubMed
  13. Roff SR, Sanou MP, Rathore MH, Levy JA, Yamamoto JK. Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects. Hum Vaccin Immunother. 2015; 11(6):1540-56.  View on PubMed
  14. Ye L, Wang J, Beyer AI, Teque F, Cradick TJ, Qi Z, Chang JC, Bao G, Muench MO, Yu J, Levy JA, Kan YW. Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Δ32 mutation confers resistance to HIV infection. Proc Natl Acad Sci U S A. 2014 Jul 01; 111(26):9591-6.  View on PubMed
  15. Venditto VJ, Wieczorek L, Molnar S, Teque F, Landucci G, Watson DS, Forthal D, Polonis VR, Levy JA, Szoka FC. Chemically modified peptides based on the membrane-proximal external region of the HIV-1 envelope induce high-titer, epitope-specific nonneutralizing antibodies in rabbits. Clin Vaccine Immunol. 2014 Aug; 21(8):1086-93.  View on PubMed
  16. Sanou MP, Roff SR, Mennella A, Sleasman JW, Rathore MH, Yamamoto JK, Levy JA. Evolutionarily conserved epitopes on human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus reverse transcriptases detected by HIV-1-infected subjects. J Virol. 2013 Sep; 87(18):10004-15.  View on PubMed
  17. Liu L, Wang L, Huang L, Siu V, Teque F, Aweeka FT, Levy JA. Nevirapine inhibits the anti-HIV activity of CD8+ cells. J Acquir Immune Defic Syndr. 2013 Jun 01; 63(2):184-8.  View on PubMed
  18. Kaushik S, Teque F, Patel M, Fujimura SH, Schmidt B, Levy JA. Plasmacytoid dendritic cell number and responses to Toll-like receptor 7 and 9 agonists vary in HIV Type 1-infected individuals in relation to clinical state. AIDS Res Hum Retroviruses. 2013 Mar; 29(3):501-10.  View on PubMed
  19. Ippolito G, Levy JA, Sonnerborg A, Mugusi F, Dianzani F. AIDS and HIV Infection after Thirty Years. AIDS Res Treat. 2013; 2013:731983.  View on PubMed
  20. Sanou MP, De Groot AS, Murphey-Corb M, Levy JA, Yamamoto JK. HIV-1 Vaccine Trials: Evolving Concepts and Designs. Open AIDS J. 2012; 6:274-88.  View on PubMed

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