Activation of Host Cellular Signaling and Mechanism of Enterovirus 71 Viral Proteins Associated with Hand, Foot and Mouth Disease

Abstract

Enteroviruses are members of the Picornaviridae family consisting of human enterovirus groups A, B, C, and D as well as nonhuman enteroviruses. Human enterovirus type 71 (EV71) has emerged as a major cause of viral encephalitis, known as hand, foot, and mouth disease (HFMD), in children worldwide, especially in the Asia-Pacific region. EV71 and coxsackievirus A16 are the two viruses responsible for HFMD which are members of group A enteroviruses. The identified EV71 receptors provide useful information for understanding viral replication and tissue tropism. Host factors interact with the internal ribosome entry site (IRES) of EV71 to regulate viral translation. However, the specific molecular features of the respective viral genome that determine virulence remain unclear. Although a vaccine is currently approved, there is no effective therapy for treating EV71-infected patients. Therefore, understanding the host-pathogen interaction could provide knowledge in viral pathogenesis and further benefits to anti-viral therapy development. The aim of this study was to investigate the latest findings about the interaction of viral ligands with the host receptors as well as the activation of immunerelated signaling pathways for innate immunity and the involvement of different cytokines and chemokines during host-pathogen interaction. The study also examined the roles of viral proteins, mainly 2A and 3C protease, interferons production and their inhibitory effects.