This model maintains a number of key benefits in approximating HIV transmission and early infection, including (i) utilization of human tissue from a site of exposure, (ii) maintenance of the natural, relevant rectal mucosal architecture26, (iii) natural distribution of tissue-resident cellular subsets and their cell-to-cell interactions, and (iv) support of direct infection with HIV-1, even in the absence of immune activating agents typically necessary for infection of peripheral blood cells (e.g. IL-2, PHA, etc.)24. The gene discussed is IL2; the disease is infection.