Abstract
A reliable disease model mimicking Enterovirus 71 (EV71) infection in humans is essential for understanding pathogenesis and for developing a safe and effective vaccine. Commonly used rodent models including mouse or rat models are not suitable for vaccine evaluation because the rodents are resistant to EV71 infection after they reach the age of 6 days. In this study, 21-day-old gerbils inoculated intraperitoneally (IP) with a non mouse-adapted EV71 strain developed neurological lesion-related signs including hind limb paralysis, slowness, ataxia and lethargy similar to those of central nervous system (CNS) infection of EV71 in humans. The infected gerbils eventually died of the neurological lesions and EV71 could be isolated from lung, liver, spleen, kidney, heart, spinal cord, brain cortex, brainstem and skeletal muscle. Significantly high virus replication was detected in spinal cord, brainstem and skeletal muscle by cellular analysis, real-time quantitative PCR (RT-PCR) and immunohistochemical staining. Histopathologic changes such as neuronal degeneration, neuronal loss and neuronophagia were observed in spinal cord, brain cortex, brainstem, and skeletal muscle along with necrotizing myositis and splenic atrophy. Gerbils that received two doses of inactive whole-virus vaccine showed no EV71-specific symptoms after challenged with EV71. In contrast, gerbils that received mock vaccination died of EV71-induced neuropathology after challenged with EV71. The result indicates that gerbils can serve as a reliable disease model for evaluating safety and efficacy of EV71 vaccine.
Highlights
Enterovirus 71 (EV71) is a neurotropic virus belonging to the genus Enterovirus in the Picornaviridae family
In the gerbils aged from 28 days to 49 days, the gerbils in the younger age group sometimes died of the EV71 infection whereas gerbils in the older age group could develop hind limb paralysis induced by EV71 infection but no death
Reported studies in rodent models revealed only newborn mice were shown to be susceptible to EV71 infection with clinical symptoms but no damage to central nervous system (CNS), and neuronal lesions could only be induced by EV71 strains that have been adapted by serial passages in mouse brains
Summary
Enterovirus 71 (EV71) is a neurotropic virus belonging to the genus Enterovirus in the Picornaviridae family. It causes outbreaks of hand, foot and mouth disease (HFMD) in young children throughout the world with a significantly increased mortality in recent years, especially in the Asia-Pacific region [1,2,3,4,5]. Since the first case reported in California in 1969 [9], EV71 has caused several large-scale outbreaks worldwide and severe neurological diseases have been commonly diagnosed in young children [1,10,11,12,13]. HFMD associated with EV71 infection is an important public health problem [15] and further understanding pathogenesis of the EV71 infection is needed to identify options for prevention and treatment of the disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
