Persistence of HIV Viral Reservoirs
Dr. Lisa Frenkel
The development of anti-retroviral therapy (ART) revolutionized HIV treatment, but discontinuing ART leads to reactivation of the infection due to persistence of viral reservoirs. Broadly, Lisa Frenkel’s research is focused on diagnostic tools for HIV and the mechanisms that allow for viral persistence, interaction with other diseases, and aspects of virus transmission.
Discovering the mechanisms for viral persistence, despite effective ART, is necessary for the potential development of a curative therapy for HIV. When the virus infects a cell, the viral genome integrates into the host cell genome. Dr. Frenkel has shown that the integration site of the virus influences the ability of the infected cell to survive and proliferate because of the disruption of a gene within the host genome. The result is clonal populations of infected cells with various viral integration sites that become the reservoirs of viral persistence, despite otherwise effective ART. Ongoing projects are focused on determining the cell phenotypes and tissue sources of HIV reservoirs and how HIV reservoir cells interact with other types of cells in the immune system.
Another ongoing area of Dr. Frenkel’s research involves the connection between HIV and cervical dysplasia caused by Human Papilloma Virus (HPV) infection. In conjunction with the Uganda Cancer Institute, Dr. Frenkel is working with patients who have both HPV and HIV infections. This project is centered on determining if HIV in the immune cells of the cervix prevents the immune system from eliminating cervical cancer caused by HPV.
Dr. Frenkel is also interested in the interaction of microchimerism and thymic presentation. While in utero, the fetus exchanges a small number of cells with the mother, which is called microchimerism. At the same time, the fetus is undergoing thymic presentation – the process that allows the immune system to identify self-antigens. Some babies recognize maternal cells as self, which allows the maternal cells to remain. Other babies do not recognize maternal cells as self and the immune system eliminates the maternal cells. Dr. Frenkel is collaborating with experts in microchimerism and cellular immunity to determine if babies that tend to recognize maternal cells as self also recognize maternally-transmitted HIV as self, allowing for immune tolerance of the virus, increased viral persistence and worse prognosis for these babies.
Dr. Frenkel would be interested in working with industry partners in development of therapies and diagnostics for HIV, including point-of-care assays. She is particularly interested in research related to the persistence of viral reservoirs during ART. In the future, by identifying drug-resistant mutations, and by discovering the mechanisms that allow for the persistence of virus reservoirs within different contexts and populations, Dr. Frenkel’s research may help improve treatment or move toward a curative therapy for HIV.
Stage of Development
- Collaborative research opportunity
- Sponsored research agreement
- Consultation agreement
- Tissue sample access
- Jourdain G, Wagner TA, Ngo-Giang-Huong N, Sirirungsi W, Klinbuayaem V, Fregonese F, Nantasen I, Techapornroong M, Halue G, Nilmanat A, Wittayapraparat P, Chalermpolprapa V, Pathipvanich P, Yuthavisuthi P, Frenkel LM, Lallemant M. Association between detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy and virologic failure. Clin Infect Dis. 2010; 50:1397-1404.
- Tobin NH, Learn GH, Holte SE, Wang Y, Melvin AJ, McKernan JL, Pawluk DM, Mohan KM, Lewis PF, Mullins JI and Frenkel LM. Evidence that Low-level Viremias During Effective HAART Result from Two Processes: Expression of Archival Virus and Replication of Virus. J Virol. 2005; 79: 9625-34.
- Wagner T, McKernan J, Tobin N, Tapia K, Mullins J, Frenkel L. An increasing proportion of monotypic HIV-1 DNA sequences during antiretroviral treatment suggests proliferation of HIV-infected cells. J Virol. 2013; 87: 1770-1778.
- Wagner TA, McLaughlin S, Garg K, Cheung CY, Larsen BB, Styrchak S, Huang HC, Edlefsen PT, Mullins JI, Frenkel LM. HIV Latency. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection. Science. 2014; 345: 570-573.
To learn more about partnering with Seattle Children’s Research Institute on this or other projects, please contact:
Dr. Elizabeth Aylward, Director
Office of Science-Industry Partnerships
Seattle Children's Research Institute
2001 8th Ave., M/S CW8-5
Seattle, WA 98121