ObjectiveTo explore the possibility that an HIV-1 gene product may modulate entry of an invasive enteric pathogen into a terminally differentiated human intestinal cell line. HIV-1 Tat was selected for investigation because of its unique ability to cross cell membranes.MethodsAfter transient transfection of HT29-C1 cells with plasmids containing HIV-1 long terminal repeat (LTR)-lacZplus a Tat expression cassette, or with a pSR-lacZcontrol plasmid, bacterial invasion assays were performed on both groups of cells utilizing a clinicalSalmonellaisolate. Assays were performed concurrently on a control group of non-transfected cells. A second series of experiments compared bacterial invasion into cells transfected with the Tat expression vector alone versus cells transfected with either an isogenic expression vector that did not make Tat, or with pSR-lacZFinally, the ability of exogenous Tat protein to transactivate an HIV-1 LTR-chloramphenicol acetyltransferase (CAT) plasmid which had been transfected into HT29-C1 cells, and to modulateSalmonellainvasion was also assessed.ResultsHT29-C1 cells transfected with a Tat expression vector, either alone or in combination with another plasmid, were significantly less susceptible to bacterial invasion than cells that either did not undergo transfection, were transfected with an otherwise isogenic expression vector without Tat, or transfected with an unrelated plasmid. Duplicate experiments also demonstrated that exogenous purified Tat protein transactivated an HIV-1 LTR-CAT plasmid which had been transfected into HT29-C1 cells, and inhibitedSalmonellainvasion compared with unexposed cells.ConclusionHIV-1 Tat inhibitsSalmonellainvasion of a human enterocyte cell line whether the protein is expressed intracellularly or provided exogenously.