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