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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 cell-adapted 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 (IL-6). Antiviral assays demonstrated that ribavirin and gamma interferon administration could significantly inhibit CVA10 replication both<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>. 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.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Hand, foot, and mouth disease cases in infancy, arising from coxsackievirus A10 (CVA10) infections, are typically benign, resolving without any significant adverse events. Severe disease and fatalities, however, can occur in some children, necessitating the development of vaccines and antiviral therapies. The present study has established a newborn-mouse model of CVA10 that, importantly, recapitulates many aspects of human disease with respect to the neuropathology and skeletal muscle pathology. We found that high levels of the proinflammatory cytokine interleukin 6 correlated with disease severity and that ribavirin and gamma interferon could decrease viral titers<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>. Whole-virus vaccines produced immune responses in adult mice, and immunized mothers conferred protection on neonates against challenge from CVA10 clinical strains. Passive immunization with high-titer antisera could also improve survival rates in newborn animals.<\/jats:p>","DOI":"10.1128\/jvi.00333-17","type":"journal-article","created":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T00:40:24Z","timestamp":1492648824000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Protective Efficacies of Formaldehyde-Inactivated Whole-Virus Vaccine and Antivirals in a Murine Model of Coxsackievirus A10 Infection"],"prefix":"10.1128","volume":"91","author":[{"given":"Zhenjie","family":"Zhang","sequence":"first","affiliation":[{"name":"Shandong Universities Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases, Taishan Medical University, Taian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaopeng","family":"Dong","sequence":"additional","affiliation":[{"name":"Shandong Universities Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases, Taishan Medical University, Taian, China"},{"name":"School of Public Health, Taishan Medical University, Taian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong Universities Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases, Taishan Medical University, Taian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Carr","sequence":"additional","affiliation":[{"name":"Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan"},{"name":"National Virus Reference Laboratory, University College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongming","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Shandong Universities Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases, Taishan Medical University, Taian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Viral Infectious Diseases Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Microbiology and Epidemiology, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujun","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Viral Infectious Diseases Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yigang","family":"Tong","sequence":"additional","affiliation":[{"name":"Beijing Institute of Microbiology and Epidemiology, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Taishan Medical University, Taian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8717-2942","authenticated-orcid":false,"given":"Weifeng","family":"Shi","sequence":"additional","affiliation":[{"name":"Shandong Universities Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases, Taishan Medical University, Taian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"855","volume-title":"Virus taxonomy","author":"Knowles NJ","year":"2011","unstructured":"Knowles NJ Hovi T Hyypia T King AMQ Lindberg AM Pallansch MA Palmenberg AC Simmonds P Skern T Stanway G Yamashita T Zell R . 2011. 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