Interleukin-4 inhibits an early phase in the HIV-1 life cycle in the human colorectal cell line HT-29

Intestinal epithelial cells are continuously in contact with the gut-associated lymphoid tissues (GALT). Gastrointestinal infection by viruses, bacteria and parasites or the presence of an inflammatory bowel disease may influence the GALT cytokine network. However, the effect of the different cytokines on susceptibility of human intestinal epithelial cells to HIV-1 infection remains undefined. We demonstrate here that IL-4 inhibits infection with reporter HIV-1 viruses pseudotyped with NDK-Env without affecting integrated proviral DNA. Furthermore, IL-4 also inhibits, in a dose-dependent manner, infection of HT-29 cells with HIV-1-based AMLV, HTLV-I and VSV-G pseudotypes. A fusion assay showed that this event is not affected by IL-4, thus suggesting that a post-fusion step is affected. A reduction in the completion of DNA retrotranscription indicates that IL-4 may affect this step, or any prior event. Altogether our data indicate that IL-4 is negatively affecting an early post-fusion step in the HIV-1 replication cycle in HT-29 cells.