Experimental workflow. This study included a tiered siRNA screening approach coupled with CRISPR-generated knockout Vero cell lines to evaluate host genes and their implication during RV infection. The primary siRNA screen was performed with pooled OTP-siRNA in MA104 cell line using the simian rotavirus strain RV3. Top hits were selected by a z-score analysis and subjected to deconvoluted validation siRNA screens in Vero cells with the rotavirus strains RV3-BB, Rotarix, CDC-9. Resulting hits were evaluated in CRISPR generated Vero cell lines with CDC-9 and Rotarix (GSK P5) strains.