In this manuscript, we used an in vivo model that faithfully recapitulates key features of HIV infection in the MGT and that permits the detailed analysis of all the individual organs of the MGT to show that (i) all MGT tissues are reconstituted with human hematopoietic cells, (ii) the human cells present in the MGT are predominantly T cells expressing CCR5, (iii) cells present throughout the entire MGT are productively infected with HIV regardless of the route of inoculation or viral isolate, and (iv) HIV infection results in CD4+ T cell depletion of MGT tissues. This evidence concerns the gene CCR5 and HIV infectious disease.