Despite these caveats, we were able to reproduce the epithelial barrier dysfunction (e.g., reduced levels of transcripts for tight junction proteins and elevated cell death) observed in prior studies during HIV infection using our organoid model, and expanded upon these findings by identifying key cytokines (IFNα, IFNγ) that are likely to be causing these changes in vivo, as well as establishing the importance of A20 levels in mediating these changes. Here, IFNG is linked to HIV infectious disease.