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作者

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

作者单位

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

刊名

Journal of Virology

年份

2017

卷号

Vol.91 No.9

ISSN

0022-538X;1098-5514

关键词

Coxsackievirus CVA6 infection Enterovirus Murine model

摘要

Hand, foot, and mouth disease is a global health concern. Family Picornaviridae members, particularly enterovirus A71 and coxsackievirus A16 , are the primary etiological agents of HFMD; however, a third enterovirus A species, CVA6, has been recently associated with epidemic outbreaks. Study of the pathogenesis of CVA6 infection and development of antivirals and vaccines are hindered by a lack of appropriate animal models. We have developed and characterized a murine model of CVA6 infection th...更多

Hand, foot, and mouth disease is a global health concern. Family Picornaviridae members, particularly enterovirus A71 and coxsackievirus A16 , are the primary etiological agents of HFMD; however, a third enterovirus A species, CVA6, has been recently associated with epidemic outbreaks. Study of the pathogenesis of CVA6 infection and development of antivirals and vaccines are hindered by a lack of appropriate animal models. We have developed and characterized a murine model of CVA6 infection that was employed to evaluate the antiviral activities of different drugs and the protective efficacies of CVA6-inactivated vaccines. Neonatal mice were susceptible to CVA6 infection via intramuscular inoculation, and the susceptibility of mice to CVA6 infection was age and dose dependent. Five-day-old mice infected with 10 5.5 50% tissue culture infective doses of the CVA6 WF057R strain consistently exhibited clinical signs, including reduced mobility, lower weight gain, and quadriplegia with significant pathology in the brain, hind limb skeletal muscles, and lungs of the infected mice in the moribund state. Immunohistochemical analysis and quantitative reverse transcription-PCR analyses showed high viral loads in skeletal muscle, and elevated levels of interleukin-6 were associated with severe viral pneumonia and encephalitis. Ribavirin and gamma interferon administered prophylactically diminished CVA6- associated pathology in vivo, and treatment with IL-6 accelerated the death of neonatal mice. Both specific anti-CVA6 serum and maternal antibody play important roles in controlling CVA6 infection and viral replication. Collectively, these findings indicate that this neonatal murine model will be invaluable in future studies to develop CVA6-specific antivirals and vaccines.收起

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