Host Serine Proteases TMPRSS2 and TMPRSS11D Mediate Proteolytic Activation and Trypsin-Independent Infection in Group A Rotaviruses
Michihito Sasaki, Yukari Itakura, Mai Kishimoto, Koshiro Tabata, Kentaro Uemura, Naoto Ito, Makoto Sugiyama, Christida E. Wastika, Yasuko Orba, Hirofumi Sawa
Abstract
Proteolytic cleavage of the viral VP4 protein is essential for virion maturation and infectivity in group A rotaviruses (RVAs). In cell culture, RVAs are propagated in culture medium supplemented with the exogenous protease trypsin, which cleaves VP4 and induces the maturation of progeny RVA virions. In this study, we demonstrated that the host proteases TMPRSS2 and TMPRSS11D mediate the trypsin-independent infection and growth of RVA. Our data revealed that the proteolytic activation of RVAs by TMPRSS2 and TMPRSS11D occurs at the viral entry step. Because TMPRSS2 and TMPRSS11D gene expression induced similar or higher levels of RVA growth as trypsin-supplemented culture, this approach offers potential advantages for RVA research and development.