Since IELs are key in targeting virus-infected IECs, via perforin, granzyme B, and IFN-γ and can perform CTL functions and secrete a broad spectrum of interferons, including types I, II, and III, supporting the antiviral state of the epithelium [45,100], we speculate that their reduced frequency is associated with impaired antiviral responses during HIV infection. This evidence concerns the gene PRF1 and HIV infectious disease.