Nicolas Sluis-Cremer, PhD, has been awarded funding of $559,118 for a one-year R56 grant by the National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) entitled “HIV-Reservoir in Naïve CD+ T cells”. This proposal was submitted in response to the competitive funding opportunity entitled NIH Research Project Grant (Parent R01) under funding opportunity number PA-18-484.
The latent reservoir in resting CD4+ T cells is viewed as a major obstacle to curing HIV-1 infection. The resting CD4+ T cell population, however, is heterogeneous and includes naïve (TN), stem cell-like memory, central memory (TCM), transitional memory (TTM), effector memory (TEM), and terminally differentiated cells. HIV-1 DNA is almost always detected in TN cells in both viremic and suppressed individuals, although with a much lower frequency compared to the TCM, TTM and TEM compartments. In light of the low infection rates of CD4+ TN cells, there has been little emphasis on studying the establishment and reversal of latency in these cells. This study focuses on the replication-competent latent HIV-1 reservoir in CD4+ naïve T cells (TN). This is an important reservoir because as much, if not more, virus is produced from TN cells compared to CD4+ central memory T cells (TCM) after exposure to latency reactivating agents, even though the frequency of HIV-1 infection is lower in TN compared to TCM cells purified from individuals on long-term suppressive antiretroviral therapy (ART).
The scientific premise of this research is that TN cells are a major reservoir of replication-competent HIV-1. This study will advance mechanistic-driven research to gain novel insights into the biology of the latent reservoir in CD4+ TN cells.