The Role of Innate Immunity in Regulating Rotavirus Replication, Pathogenesis, and Host Range Restriction and the Implications for Live Rotaviral Vaccine Development

Rotaviruses (RVs) are important causative agents of viral gastroenteritis in the young of most mammalian species studied, including humans, in which they are the most important cause of severe gastroenteritis worldwide despite the availability of several safe and effective vaccines. Replication of RVs is restricted in a host species-specific manner, and this barrier is determined predominantly by the host interferon (IFN) signaling and the ability of different RV strains to successfully negate IFN activation and amplification pathways. In addition, viral attachment to the target intestinal epithelial cells also regulates host range restriction. Several studies have focused on the role of the innate immune response in regulating RV replication and pathogenesis. The knowledge accrued from these efforts is likely to result in rational attenuation of RV vaccines to closely match circulating (and host species-matched) virus strains. In this chapter, we review prevalent models of RV interactions with innate immune factors, viral strategies employed to regulate their function, and the implications of these findings for improved RV vaccine development.