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Enterovirus 71 infection impairs the reproductive capacity of female mice.

ABSTRACT: Enterovirus 71 (EV71) is a major cause of hand, foot and mouth disease (HFMD); however, no clinically approved vaccine or antiviral treatment is currently available for EV71 infection. In the present study, a murine model of EV71 infection was constructed. The clinical isolates of EV71 were amplified in Vero cells and used to challenge adult mice via hydrodynamic injection (HI) and intraperitoneal injection (IP). Following two challenges, >50% of the mice succumbed to EV71 infection. Surviving female mice were identified to have impaired fertility and their litter sizes were significantly decreased compared with the control group. The antibody against EV71-VP1 persisted in the sera of female mice at a high titer for >2 years after challenge. The maternal antibody in the offspring sera also persisted for ~1 year and disappeared after ~2 years. Results from the present study suggest that a high titer of active EV71 was able to impair the reproductivity of adult female mice, and that high levels of maternal antibody persisted in the offspring and protected postnatal mice from EV71-induced mortality. The promising antigenicity, immunogenicity and reactogenicity of EV71 suggests that it a potential vaccine target that may be beneficial to the control of HFMD, through immunizing infants and women of reproductive age.

SUBMITTER: Qin B

PROVIDER: S-EPMC5488539 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Enterovirus 71 infection impairs the reproductive capacity of female mice.

Qin Bo B Yan Qiuyue Q Chen Xing X Xu Xiuping X Wang Yanan Y Chen Jinkun J Dong Xuejun X

Experimental and therapeutic medicine 20170523 1

Enterovirus 71 (EV71) is a major cause of hand, foot and mouth disease (HFMD); however, no clinically approved vaccine or antiviral treatment is currently available for EV71 infection. In the present study, a murine model of EV71 infection was constructed. The clinical isolates of EV71 were amplified in Vero cells and used to challenge adult mice via hydrodynamic injection (HI) and intraperitoneal injection (IP). Following two challenges, >50% of the mice succumbed to EV71 infection. Surviving f ...[more]

PMID: 28672946

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Project description:Non-polio enteroviruses, including enterovirus 71 (EV71), have caused severe and fatal cases of hand, foot and mouth disease (HFMD) in the Asia-Pacific region. The development of a vaccine or antiviral against these pathogens has been hampered by the lack of a reliable small animal model. In this study, a mouse adapted EV71 strain was produced by conducting serial passages through A129 (?/? interferon (IFN) receptor deficient) and AG129 (?/?, ? IFN receptor deficient) mice. A B2 sub genotype of EV71 was inoculated intraperitoneally (i.p.) into neonatal AG129 mice and brain-harvested virus was subsequently passaged through 12 and 15 day-old A129 mice. When tested in 10 week-old AG129 mice, this adapted strain produced 100% lethality with clinical signs including limb paralysis, eye irritation, loss of balance, and death. This virus caused only 17% mortality in same age A129 mice, confirming that in the absence of a functional IFN response, adult AG129 mice are susceptible to infection by adapted EV71 isolates. Subsequent studies in adult AG129 and young A129 mice with the adapted EV71 virus examined the efficacy of an inactivated EV71 candidate vaccine and determined the role of humoral immunity in protection. Passive transfer of rabbit immune sera raised against the EV71 vaccine provided protection in a dose dependent manner in 15 day-old A129 mice. Intramuscular injections (i.m.) in five week-old AG129 mice with the alum adjuvanted vaccine also provided protection against the mouse adapted homologous strain. No clinical signs of disease or mortality were observed in vaccinated animals, which received a prime-and-boost, whereas 71% of control animals were euthanized after exhibiting systemic clinical signs (P<0.05). The development of this animal model will facilitate studies on EV71 pathogenesis, antiviral testing, the evaluation of immunogenicity and efficacy of vaccine candidates, and has the potential to establish correlates of protection studies.

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Enterovirus 71 infection impairs the reproductive capacity of female mice.

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Enterovirus 71 infection impairs the reproductive capacity of female mice.

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