Photo of Dr. Ott

David E. Ott, Ph.D.

Retrovirus-Cell Interaction Section

Leidos Biomedical Research, Inc.
Frederick National Laboratory for Cancer Research
Frederick, MD 21702-1201

Tel: 301-846-5723
Fax: 301-846-7119
Email: ottde@mail.nih.gov

ACVP cellular proteins in HIV-1 database
This ACVP website catalogs the cellular proteins found in the HIV-1 virions and contains recent protocols for subtilisin digestion and CD45 immunoaffinity depletion.

Biography

Dr. Ott received his Ph.D. in molecular biology in 1987 from the State University of New York at Stony Brook. He began studying retroviruses as a postdoctoral fellow in the laboratory of Dr. Alan Rein at the Frederick National Laboratory for Cancer Research. After working on retroviral-mediated human gene therapy in private industry, Dr. Ott joined the AIDS and Cancer Virus Program in 1993 and was named the head of the Retrovirus-Cell Interaction Section in 1999.

Research Description

The Retrovirus-Cell Interaction Section seeks to study the interactions between AIDS viruses and their host cells with experiments using both the HIV-1/human T cell and SIV/ rhesus macaque T cell systems. The SIV/rhesus macaque model for HIV-1 infection and disease is used by many groups in the ACVP and is an especially important as a unique in vivo model for AIDS virus immunology and pathology.

In one of the two main projects, we study aspects of AIDS virus infection of CD4+ T cells. Our studies examining human CD4+ T cells isolated from PBMC obtained from various donors detected an intrinsic resistance to productive HIV infection by a sizable fraction (~25%) of cells. Working together with the Retroviral Immunology Section, we have observed a similar phenomenon in a subset of rhesus macaque CD4+ T cells. Understanding this intrinsic resistance promises to uncover mechanisms for prevention of infection, possibly providing opportunities for therapeutic anti-viral approaches. Another research topic being investigated by our Section is restriction of HIV-1 and SIV replication by African green monkey TRIM5ɑ. We have found that retroviral transduction of African green monkey TRIM5ɑ genes into CD4+ T-cells can provide very potent restriction of both HIV-1 and SIV replication (2-3 log reductions). Combining transfer of African green monkey TRIM5ɑ restriction into CD4+ rhesus T cells that also exhibit intrinsic resistance generates cells that are highly resistant to viral replication for use in both in vitro and in vivo immunological studies using the SIV/ rhesus macaque model. Additionally a better understanding of the nature of TRIM5ɑ restriction could also provide for ways to prevent or limit HIV-1 infection in vivo.

Our second emphasis is to examine the basis of effective anti-AIDS virus T-cell responses using genetic engineering. Working closely with the Retroviral Immunology Section, we develop and use both retroviral and lentiviral vectors to transfer genes of interest into cells to examine aspects of immunology and virology that cannot be addressed using material found in nature. Approaches developed and used include studies that transfer genes into T cells for the following studies using retroviral and lentiviral vectors:

  • the hTERT gene to produce T cells with extended life-spans for long term studies
  • anti-viral T-cell receptor genes for studies that seek to identify the correlates of T-cell receptor affinity and T-cell effector function on common and comparable T-cell backgrounds
  • T-cell receptor genes to enable in vivo assessment of anti-viral function by virus-specific T cells in the SIV/rhesus macaque model
  • T-cell homing marker genes to direct adoptively transferred T cells to specific tissues that are important for immunological function.
  • shRNAs specific against T-cell effector protein genes for knockdown studies to directly evaluate the contributions of the various effector molecules to AIDS virus control.

These approaches provide the basis with which to address important aspects of AIDS virus immunology using the SIV/rhesus macaque model and HIV-1 and to better understand immune control of AIDS viruses. We also work closely with the Viral Oncology Section examining Kaposi’s sarcoma-associated herpes virus biology by engineering retroviral vectors for expression of viral microRNAs in human cells for gene regulation experiments and for human viral immunology studies using our T-cell receptor transfer system.

Key Collaborators

  • Other ACVP Sections
  • Ettore Appella, CCR NCI
  • Daniel Appella, NIDDK
  • Daniel Douek, VRC, NIAID

Recent Publications

  1. Votteler J, Neumann L, Hahn S, Hahn F, Rauch P, Schmidt K, Studtrucker N, Solbak SMO, Fossen T, Henklein P, Ott DE, Holland G, Bannert N, Schubert U: Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Retrovirology 16:8-11, 2011. PMID: 21324168
  2. Barsov EV: Telomerase and primary T cells: Biology and immortalization for adoptive immunotherapy. Immunotherapy 3(3):407-421, 2011. PMID: 21395382
  3. Minang JT, Trivett MT, Barsov EV, Del Prete GQ, Trubey CM, Thomas JA, Gorelick RJ, Piatak M Jr, Ott DE, Ohlen C: TCR triggering transcriptionally downregulates CCR5 expression on rhesus macaque CD4+ T cells with no measurable effect on susceptibility to SIV infection. Virology 409(1):132-140, 2011. Epub 2010 Oct 28. PMID: 21035160
  4. Minang JT, Trivett MT, Bolton DL, Trubey CM, Estes JD, Li Y, Smedley J, Pung R, Rosati M, Jalah R, Pavlakis GN, Felber BK, Piatak M Jr, Roederer M, Lifson JD, Ott D, Ohlen C: Distribution, persistence and efficacy of adoptively transferred central and effector memory-derived autologous SIV-specific CD8+ T cell clones in rhesus macaques during acute infection. J Immunol 184(1):315-326, 2010. Epub 2009 Nov 30. PMID: 19949091.
  5. Miller Jenkins LM, Ott DE, Hayashi R, Coren LV, Wang D, Xu Q, Schito ML, Inman JK, Appella DH, Appella E. Small-molecule inactivation of HIV-1 NCp7 by repetitive intracellular acyl transfer. Nat Chem Biol 6(12):887-889, 2010. Epub 2010 Oct 17. PMID: 20953192
  6. Ott DE: Purification of HIV-1 virions by subtilisin digestion or CD45 immunoaffinity depletion for biochemical studies. Methods Mol Biol 485:15-25, 2009.
  7. Ott DE, Coren LV, Shatzer T: The nucleocapsid region of HIV-1 Gag assists in the coordination of assembly and gag processing: Role for RNA-Gag binding in the early stages of assembly. J Virol 83:7718-7727, 2009.
  8. Sorin M, Cano J, Davies KP, Mathew S, Shi X, Wu X, Cheng GSW, Ott D, Kalpana GV: Recruitment of a SAP18-HDAC1 complex into HIV-1 virions and its requirement for viral replication. PLoS Pathog 5(6):e1000463, 2009.
  9. Minang JT, Trivett MT, Coren LV, Barsov EV, Piatak MJr, Ott DE, Ohlen C: Nef-mediated MHC class I down-regulation unmasks clonal differences in virus suppression by SIV-specific CD8+ T cells independent of IFN-gamma and CD107a responses. Virology 391:130-139, 2009.
  10. Gousset K, Ablan SD, Coren LV, Ono A, Soheilian F, Nagashima K, Ott DE, Freed EO: Real-time visualization of HIV-1 GAG trafficking in infected macrophages. PLoS Pathogens 4:1-14, 2008.
  11. Minang JT, Barsov EV, Yuan F, Trivett MT, Piatak M, Lifson JD, Ott DE, Ohlen C: Efficient inhibition of SIV replication in rhesus CD4+ T-cell clones by autologous immortalized SIV-specific CD8+ T-cell clones. Virology 372:430-441, 2008.
  12. Coren LV, Shatzer T, Ott DE: CD45 immunoaffinity depletion of vesicles from Jurkat T cells demonstrates that "exosomes" contain CD45: no evidence for a distinct exosome/HIV-1 budding pathway. Retrovirology 5:64, 2008.
  13. Ott DE: Cellular proteins detected in HIV-1. Rev Med Virol 18:159-175, 2008.
  14. Chan R, Uchil PD, Jin J, Shui G, Ott DE, Mothes W, Wenk MR: Retroviruses human immunodeficiency virus and murine leukemia virus are enriched in phosphoinositides. J Virol 82:11228-11238, 2008.
  15. Thomas JA, Ott DE, Gorelick RJ: Efficiency of HIV-1 postentry infection processes: Evidence against disproportionate numbers of defective virions. J Virol 81:4367-4370, 2007.
  16. Coren LV, Thomas JA, Chertova EN, Sowder RC, II, Gagliardi TD, Gorelick RJ, Ott DE: Mutational analysis of the C-terminal gag cleavage sites in human immunodeficiency virus type 1. J Virol 81:10047-10054, 2007.
  17. Andersen H, Barsov EV, Trivett MT, Trubey CM, Giavedoni LD, Lifson JD, Ott DE, Ohlen C: Transduction with human telomerase reverse transcriptase immortalizes a rhesus macaque CD8+ T cell clone with maintenance of surface marker phenotype and function. AIDS Res Hum Retroviruses 23:456-465, 2007.
  18. Xu H, Chertova E, Chen J, Ott DE, Roser JD, Hu W-S, Pathak VK: Stoichiometry of the antiviral protein APOBEC3G in HIV-1 virions. Virology 360:247-256, 2007.
  19. Melar M, Ott DE, Hope TJ: Physiological levels of virion-associated HIV-1 envelope induce coreceptor-dependent calcium flux. J Virol 81:1773-1785, 2007.

Staffing

  • Eugene Barsov, M.D., Ph.D., Visiting Scientist
  • Lori V. Coren, Research Associate II