Resistance of echovirus 11 to ClO2 is associated with enhanced host receptor use, altered entry routes and high fitness

Previous studies have shown that waterborne viruses could exhibit resistance to common water disinfectants. We generated echovirus 11 (E11) with resistance to chlorine dioxide (ClO2) and UVC using an experimental evolution approach, and we characterized the underlying phenotypic and genotypic changes. The ClO2-resistance of E11 was linked to an improved capacity of the virus to its host cells. Specifically, certain viruses accumulated mutations that caused amino acid substitutions from ClO2-labile to ClO2-stable residuals. Furthermore, the ClO2-resistant mutants could bind better to alternative receptors. The UVC-resistance of E11 was manifested by a shift from first-order to biphasic inactivation kinetics. Interestingly, the adaptation to UVC was accompanied by a decrease in the virus mutation rate, and resistance to ribavirin. Remarkably, the evolved populations also demonstrated a fitness advantage comparing to the less resistant wild-types. Overall our study contributes to a better understanding of the mechanism underlying disinfection resistance in enteroviruses.