Cholera toxin inhibits HIV-1 replication in human colorectal epithelial HT-29 cells through adenylate cyclase activation

Mixed feeding, combining breast milk and nonhuman milk and/or solid food, is a common practice in developing countries that increases the risk of vertical HIV-1 transmission. It also enhances the risk of infection by waterborne microorganisms such as Vibrio cholerae, a diarrhoea-causing pathogen that frequently infects children below 18 months of age. Although both HIV-1 and V. cholerae affect young children and target intestinal epithelial cells, no information is currently available on possible interactions between these two pathogens. In this study, we show for the first time that cholera toxin (CTx), at a concentration as low as 100 pg/ml, inhibits HIV-1 infection of HT-29, a human colorectal epithelial cell line. The CTx-mediated inhibitory effect does not result from a down-regulation of receptor/co-receptor expression or a modulation of viral transcription. Nevertheless, additional experiments indicate that a yet to be identified early step in the virus life cycle is targeted by CTx since the enterotoxin similarly reduces infection of HT-29 cells with AMLV-I, HTLV-I and HIV-1 pseudotyped viruses while exerting no effect on infection with VSV-G pseudotypes. Furthermore, our results indicate that the CTx-dependent suppression is not due to the cholera toxin subunit B but linked instead to the action of cholera toxin subunit A (CTA). Altogether our data indicate that the CTA subunit of CTx is negatively affecting an early event in HIV-1 replication in human colon cancer HT-29 cells.