Basic Science Award

Although macrophages are important in vivo targets for Human Immunodeficiency Virus Type 1 (HIV-1) infection, their relevance for the transmission, spread, and pathogenesis of HIV-1 remains unclear. This may be due to heterogeneity in subpopulations of macrophages, such that some but not all are permissive for infection. In part, this tropism could be related to tissue localization, but cell-intrinsic restriction factors, such as APOBEC3 and SAMHD1, have also recently been shown to exhibit direct antiviral activity. The objectives of this proposal are to survey human tissue macrophages and to delineate potential heterogeneity amongst subpopulations using surface and transcriptional phenotypes. These data will then be analyzed in conjunction with HIV-1 infectivity data to determine whether some but not all macrophage subpopulations are permissive to infection and whether such differences in susceptibility correlate with the expression of known and potentially undiscovered restriction factors.