Abstract
Enterovirus 71 (EV71) is a global health threat. Children infected with EV71 could develop hand-foot-and-mouth disease (HFMD), encephalitis, paralysis, pulmonary edema, and death. At present, no effective treatment for EV71 is available. We reviewed here various mouse models for EV71 pathogenesis and therapy. Earlier studies relied on the use of mouse-adapted EV71 strains. To avoid artificial mutations arising de novo during the serial passages, recent studies used EV71 clinical isolates without adaptation. Several human receptors for EV71 were shown to facilitate viral entry in cell culture. However, in vivo infection with human SCARB2 receptor transgenic mice appeared to be more limited to certain strains and genotypes of EV71. Efficacy of oral infection in these transgenic models is extremely low. Intriguingly, despite the lack of human receptors, immunodeficient neonatal mouse models can still be infected with EV71 clinical isolates via oral or intraperitoneal routes. Crossbreeding between SCARB2 transgenic and stat1 knockout mice generated a more sensitive and user-friendly hybrid mouse model. Infected hybrid mice developed a higher incidence and earlier onset of CNS disease and death. Different pathogenesis profiles were observed in models deficient in various arms of innate or humoral immunity. These models are being actively used for antiviral research.
Highlights
Enterovirus 71 (EV71 or EV-A71) was first isolated from the stool of encephalitis patients in California in 1969 [1]
The hSCARB2 Tg mice are similar to the NOD/SCID mice in supporting the replication of muscle-tropic EV71. Neither model of these hSCARB2 Tg mice has so far been shown to support efficient oral infection, which is a major route for transmission in children [51,52]. Before these models are shown to be susceptible to a broader source of different clinical isolates and genotypes, it is a caveat to carefully choose the best EV71 strains in the experimental design based on the hSCARB2 transgenic model
In 2018, there are many issues that need to be solved in the modeling of EV71 infection and pathogenesis
Summary
Enterovirus 71 (EV71 or EV-A71) was first isolated from the stool of encephalitis patients in California in 1969 [1] It is a positive-strand RNA virus, belonging to the Picornaviridae family [2,3]. RNA viruses, it contains an IRES element, which drives the translation of a polyprotein from a 7.4 kb genomic mRNA template Upon protease cleavage, this polyprotein precursor can convert into various smaller-size structural and non-structural proteins, leading to capsid assembly. In a long-term study, EV71-infected patients with CNS involvement and/or failure was associated with delayed neurodevelopment and reduced cognitive functioning [7]. Like children in this poliovirus in century. We compare below their respective advantages, limitations, and caveats in using pathogenesis. We compare below their respective advantages, limitations, and caveats in using these models
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