HIV Infections and Dendritic Cells in a Post-Antiretroviral Therapy Era

Objective. To determine whether gene expression in myeloid dendritic cells (mDC) is correlated to the size of the human immunodeficiency virus (HIV) reservoir in CD4 T cells during antiretroviral therapy (ART)-treated HIV infections. Background. mDC are innate immune cells that respond to viral infections. One barrier to curing HIV infections is the existence of latent reservoirs after HIV integrates into the genome of CD4 T cells. There is a critical need to examine the role of mDC in viral reservoir maintenance to inform strategies to counteract HIV latency. Methods. We will quantify the HIV reservoir in CD4 T cells and assess the gene expression of mDCs from successfully ART-treated (ST) individuals. Using these data, we will develop a computational approach to model the relationship between mDC gene expression and the size of HIV reservoirs in CD4 T cells. Results. We identified genes and pathways in mDC that correlated with HIV reservoir levels in CD4 T cells, which differed depending on treatment status. We anticipate that a larger cohort of ST subjects will enable the further identification of genes and pathways of mDC that correlate with HIV reservoir levels. Conclusion. These results will inform targets for the control or elimination of latent reservoirs in HIV curative approaches. This work has the potential to identify new biomarkers for determining reservoir size and inform strategies such as DC vaccination regimes for eradicating viral reservoirs during HIV infections. Grants. The Institute of AIDS and Emerging Infectious Diseases (IAEID) Pilot Grant, Florida Department of Health, awarded to Shannon Murray