Basic Science of Mucosal Immunity and Viral Persistence
Understanding HIV Tissue Reservoirs and Immunology of Mucosal Sites
Persistence of HIV in mucosal sites may provide a significant reservoir for HIV, even in patients undergoing ART therapy, and might act as a barrier to a cure. Dr. Bull has been studying factors that promote persistence and replenishment of the reservoir, including defining the immunological environment within mucosal sites, assessing viral dynamics and shedding, and the potential contribution of other chronic viruses to the maintenance of reservoirs. Much of Dr. Bull’s work has focused on HIV in the female genital tract, where she is focused on defining immune T cell populations and understanding the factors that affect viral RNA shedding and reservoir maintenance.
Co-infection with other chronic viruses, particularly herpesviruses including HSV-1, HSV-2, CMV and EBV, is very common in HIV-infected individuals. Dr. Bull is investigating the role of these infections in HIV reservoir persistence to investigate the hypothesis that the immune response to these co-infecting viruses results in CD4+ T cell proliferation and a subsequent increase in reservoir size. She is studying the relationship between subclinical herpes shedding and HIV DNA concentration, cytokine production and HIV envelop diversity to gain a better understanding of the role of these coinfections in promoting HIV persistence.
Dr. Bull’s research evaluates the role of CD4+ regulatory T cells during HIV infection, and explores the role of this population of cells in the context of vaccines. She is interested in studying whether vaccines given to people shift their T cell profile toward a more suppressive state, which would potentially make a vaccine less effective. Given Dr. Bull’s expertise in mucosal tissues and the immunologic environment in mucosal sites, she would be interested in industry collaborations focused on gaining a better understanding of the impact of and interplay between systemic vaccines and mucosal sites.
Stage of Development
- Human blood & tissue pre-clinical trials
- Human blood & tissue clinical trials
- Collaborative research opportunity
- Sponsored research agreement
- Consultation agreement
- Bull M., Soria J, Ticona E, et al. Monotypic low-level HIV viremias during antiretroviral therapy are associated with disproportionate production of X4 virions and systemic immune activation. AIDS. 2018; 32:1389-1401.
- Ticona E, Bull M, Soria J, Legard J, Styrchak S, Williams C, Mitchell C, Rosa A, Coombs R, Frenkel L. Biomarkers of inflammation in HIV-infected Peruvian men and women before and during suppressive antiretroviral therapy. AIDS. 2015;29(13):1617-1622.
- Bull M, Legard J, Tapia K, Sorensen B, Cohn S, Garcia R, Holte S, Coombs R, Hitti J. HIV-1 Shedding From the Female Genital Tract is Associated With Increased Th1 Cytokines/Chemokines That Maintain Tissue Homeostasis and Proportions of CD8+FOXP3+ T Cells. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2014;67(4):357-364.
- Bull M, Heath L, McKernan-Mullin J, Kraft K, Acevedo L, Hitti J, Cohn S, Tapia K, Holte S, Dragavon J, Coombs R, Mullins J, Frenkel L. Human Immunodeficiency Viruses Appear Compartmentalized to the Female Genital Tract in Cross-Sectional Analyses but Genital Lineages Do Not Persist Over Time. Journal of Infectious Diseases. 2013;207(8):1206-1215.
- Bull M, Learn G, Genowati I, Mckernan J, Hitti J, Lockhart D, Tapia K, Holte S, Dragavon J, Coombs R, Mullins J, Frenkel L. Compartmentalization of HIV-1 within the Female Genital Tract Is Due to Monotypic and Low-Diversity Variants Not Distinct Viral Populations. PLoS ONE. 2009;4(9):e7122.