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作者

Zhang, Z. Dong, Z. Li, J. Carr, M.J. Zhuang, D. Wang, J. Zhang, Y. Ding, S. Tong, Y. Li, D. Shi, W.

作者单位

National Virus Reference Laboratory, University College Dublin, Dublin, Ireland a Shandong Universities Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases, Taishan Medical University, Taian, China Department of Viral Infectious Diseases Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China f School of Public Health, Taishan Medical University, Taian, China Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan Beijing Institute of Microbiology and Epidemiology, Beijing, China

刊名

Journal of Virology

年份

2017

卷号

Vol.91 No.13

ISSN

0022-538X;1098-5514

关键词

Antiviral Coxsackievirus A10 HFMD Mouse model Vaccine

摘要

Coxsackievirus A10 is one of the major pathogens associated with hand, foot, and mouth disease . CVA10 infection can cause herpangina and viral pneumonia, which can be complicated by severe neurological sequelae. The morbidity and mortality of CVA10-associated HFMD have been increasing in recent years, particularly in the pan-Pacific region. There are limited studies, however, on the pathogenesis and immunology of CVA10-associated HFMD infections, and few antiviral drugs or vaccines have been r...更多

Coxsackievirus A10 is one of the major pathogens associated with hand, foot, and mouth disease . CVA10 infection can cause herpangina and viral pneumonia, which can be complicated by severe neurological sequelae. The morbidity and mortality of CVA10-associated HFMD have been increasing in recent years, particularly in the pan-Pacific region. There are limited studies, however, on the pathogenesis and immunology of CVA10-associated HFMD infections, and few antiviral drugs or vaccines have been reported. In the present study, a celladapted CVA10 strain was employed to inoculate intramuscularly 5-day-old ICR mice, which developed significant clinical signs, including reduced mobility, lower weight gain, and quadriplegia, with significant pathology in the brain, hind limb skeletal muscles, and lungs of infected mice in the moribund state. The severity of illness was associated with abnormally high expression of the proinflammatory cytokine interleukin 6 . Antiviral assays demonstrated that ribavirin and gamma interferon administration could significantly inhibit CVA10 replication both in vitro and in vivo. In addition, formaldehyde-inactivated CVA10 whole-virus vaccines induced immune responses in adult mice, and maternal neutralizing antibodies could be transmitted to neonatal mice, providing protection against CVA10 clinical strains. Furthermore, high-titer antisera were effective against CVA10 and could relieve early clinical symptoms and improve the survival rates of CVA10-challenged neonatal mice. In summary, we present a novel murine model to study CVA10 pathology that will be extremely useful in developing effective antivirals and vaccines to diminish the burden of HFMD-associated disease.收起

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