Retrovirus-Cell Interaction Section
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 our 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. 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. In addition to intrinsic resistance, our Section also studies extrinsic restriction of HIV-1 and SIV replication, notably resistance to infection induced by ectopic expression of 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). Molecularly engineering African green monkey TRIM5ɑ restriction into CD4+ rhesus T cells generates cells that are highly resistant to viral replication and suitable for use in both in vitro and in vivo immunological studies using the SIV/ rhesus macaque model. Additional studies, focusing on the mechanism of the elite suppression induced by African green monkey TRIM5ɑ, could lead to a better understanding of the nature of TRIM5ɑ restriction that suggests 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 Pathogenesis Section, we use both retroviral and lentiviral vectors to transfer genes of interest into cells to provide “designer” cells to test aspects of immunology and virology for both in vitro and in vivo studies. 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.
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 the cellular immune response to Kaposi’s sarcoma-associated herpes virus with our suite of immunology and T-cell engineering experiments using our T-cell receptor transfer system.
- Other ACVP Sections
- Ettore Appella, CCR NCI
- Daniel Appella, NIDDK
- Daniel Douek, VRC, NIAID
Retrovirus-Cell Interaction Section Staff
David E. Ott, Ph.D.
- Burke, Daniel
- Cohen, Lori