Una O'Doherty
Assistant Professor, Dept of Pathology and Laboratory Medicine

Microbiology, Virology and Parasitology Program

Address

265 John Morgan
3620 Hamilton Walk
Philadelphia, PA 19104

Office tel.: 215 573-7273
Lab tel.: 215 573-7781
Fax: 215 573-0879
E-mail: unao@mail.med.upenn.edu

Link(s)

Dr. O'Doherty's Lab webpage

Education

Barnard College: BA (Biochemistry), 1987.

Rockefeller University: PhD (Cellular immunology), 1994.

Cornell Univeristy Medical College: MD (Medicine), 1995.

Research Interests

• HIV-1 latency.

Key words: HIV, latency, reservoirs, dendritic cells, viral pathogenesis, proviral integration, retrovirus, virology, T cell activation, resting T cells.

Search PubMed for articles

Description of Research

Highly active anti-retroviral therapy can clear the blood of HIV-1 virions. But, despite long-term suppression of virus, when the drugs are stopped the virus returns. Thus, reservoirs of latent, treatment-resistant HIV-1 exist in infected individuals and are a major barrier to cure. Our lab has developed an in vitro model of HIV-1 latency. We use quantitative and imaging methods to study how HIV-1 establishes latent infection in resting CD4+ T cells.

Current dogma holds that latent HIV-1 infection occurs only when T cells are activated. Our findings challenge this. Using novel quantitative assays we made three discoveries about latent HIV-1 infection in CD4+ T cells. One, HIV-1 can integrate into resting CD4+ T cells. Two, the T cells bearing integrated HIV-1 genomes do not produce new virions unless stimulated. Three after stimulation a percentage of these cells produce virus. Thus, in our system HIV-1 establishes latent infection in resting T cells in the absence of activating stimuli. We now want to determine if reservoirs form more efficiently in the presence of subtle stimuli and if reservoirs form preferentially in subsets of resting T cells that are more permissive for HIV-1 integration.

In summary, we have developed an in vitro model of HIV-1 latency and our studies promise to provide new insights into reservoir formation in HIV-1 infected individual and may eventually lead to novel therapies.

Recent Publications

O’Doherty U, Swiggard WJ, and Malim MH. Human Immunodeficiency Virus type 1 spinoculation enhances infection through virus binding. J. Virol. 74(21): 10074-10080 (2000).

O'Doherty U, Swiggard WJ, Jeyakumar D, McGain D, and Malim MH. A sensitive, quantitative assay for HIV-1 integration. J. Virol. 76(21) 10,942-10,950 (2002).

O'Doherty U, Swiggard WJ, McGain D, Jeyakumar D, and Malim MH. Late HIV-1 reverse transcripts accumulate stably within resting CD4+ T cells, but are degraded within activated T cells. AIDS Res. Hum. Retroviruses 20(3): 285-295 (2004).

O'Doherty U,. Mechanisms of Human Immunodeficiency Virus type 1 latency. Transfusion. 45 (Suppl): 88S-91S (2005).

Swiggard WJ, Baytop C, Yu JJ, Dai J, Li C, Schetzenmair R, Theodosopoulos T, O'Doherty U. Human Immunodeficiency Virus type 1 can establish latent infection in resting CD4+ T cells in the absence of activating stimuli. J.Virol. in press (2005).

Lab

Rotation Projects for 2006-2007

1. Measure the percentage of resting T cells that contain provirus (integrated viral DNA) in HIV-infected individuals in various CD4+ T cell subpopulations including memory and naïve subsets.
2. Quantify the frequency of multiply infected cells after single round infection of resting CD4+ T cells.
3. Identify the insertion sites of proviral DNA within resting CD4+ T cells.
4. Determine the susceptibilities of other primary WBC (dendritic cells and progenitor cells to HIV integration).

Lab personnel:

Jihong Dai - Postdoctoral Fellow
Jenny Yu - Research Specialist
Cliff Baytop - Research Specialist