INTERFERON-GAMMA AND INTERLEUKIN-1, BUT NOT INTERFERON-ALFA, INHIBIT ROTAVIRUS ENTRY INTO HUMAN INTESTINAL-CELL LINES

Background & Aims: Rotavirus, an important agent of gastroenteritis in children, causes diarrhea by infecting differentiated villus enterocy tes in the small intestine. The aim of this study was to determine whe ther cytokines that can be expressed by mucosal cells have an effect o n the rotavirus susceptibility of cultured human enterocytes. Methods: Caco-2 and HT-29 cells were pretreated with various cytokines before challenge with rotavirus. Results: Interleukin (IL)-1, interferon (IFN )-alpha, and IFN-gamma pretreatment led to a dose-dependent resistance to rotavirus infection. Maximum effects occurred after 72 hours of pr etreatment, whereas no detectable inhibition occurred with <12 hours o f pretreatment. Liposomal transfection of single-shelled and double-sh elled rotavirus particles bypassed the block to rotavirus replication in IFN-gamma- and IL-1-treated but not IFN-alpha-treated cells, Bindin g studies with purified, metabolically labeled rotavirus showed no sig nificant difference among IFN-gamma- and IFN-alpha-treated and control Caco-2 cells. Viral entry into Caco-2 cells was significantly inhibit ed by IFN-gamma and IL-1 but not IFN-alpha. Conclusions: IFN-alpha and IFN-gamma induce rotavirus resistance by different mechanisms, sugges ting that cytokines play a role in host defense against viral agents b y changing the phenotype of intestinal epithelial cells.