Inhibitory effect of natural interferon alpha on human immunodeficiency virus type 1 transmission from epithelial cells to lymphocytes in vitro

Abstract

The in vitro effect of human natural interferon alpha (IFN-alpha) on cell contact-mediated human immunodeficiency virus type 1 (HIV-1) transmission from epithelial cells to lymphocytes was examined. This type of infection is most likely to occur when the mucosal linings of the reproductive or digestive organs serve as latent viral reservoirs and HIV-1 invades the host through the basolateral surface of polarized epithelia upon contact with intraepithelial lymphocytes. The cell-to-cell infection model consisted of target MOLT-4 T lymphocytes exposed for various time periods to chronically HIV-1-infected intestinal monolayers (I407/YH5) in the presence of log10 dilutions of IFN (range 10(5)-10(-2) IU/ml). Concurrent measurements of resulting productive infection from MOLT-4 revealed that complete inhibition of reverse transcriptase activity was prevented by doses starting from 1 IU, whereas the cessation of p24 production occurred at 1000 IU of IFN present at inoculation. The results indicate that IFN can efficiently prevent not only cell-free but also cell-mediated HIV-1 infection--an important means of viral spread in vivo pertinent to HIV-1 transmission resulting from mucosa-lymphocyte interaction.