A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs
ABSTRACTCoxsackievirus A4 (CVA4) infection can cause hand, foot and mouth disease (HFMD), an epidemic illness affecting neonatal and paediatric cohorts, which can develop to severe neurological disease with high mortality. In this study, we established the first ICR mouse model of CVA4 infection for...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2019.1673135 |
| _version_ | 1797385764039819264 |
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| author | Zhenjie Zhang Xingcheng Zhang Michael J. Carr Hong Zhou Juan Li Shaoqiong Liu Tao Liu Weijia Xing Weifeng Shi |
| author_facet | Zhenjie Zhang Xingcheng Zhang Michael J. Carr Hong Zhou Juan Li Shaoqiong Liu Tao Liu Weijia Xing Weifeng Shi |
| author_sort | Zhenjie Zhang |
| collection | DOAJ |
| description | ABSTRACTCoxsackievirus A4 (CVA4) infection can cause hand, foot and mouth disease (HFMD), an epidemic illness affecting neonatal and paediatric cohorts, which can develop to severe neurological disease with high mortality. In this study, we established the first ICR mouse model of CVA4 infection for the evaluation of inactivated vaccines and antiviral drug screening. The CVA4 YT226R strain was selected to infect the neonatal mice and three infectious factors were optimized to establish the infection model. The 3-day-old neonatal mice exhibited clinical symptoms such as hind limb paralysis and death. The severe inflammatory reactions were closely related to the abnormal expression of the acute phase response proinflammatory cytokine IL-6 and an imbalance in the IFN-γ/IL-4 ratio. Importantly, the inactivated CVA4 whole-virus vaccine induced humoral immune responses in adult females and the maternal antibodies afforded mice complete protection against lethal dose challenges of homologous or heterologous CVA4 strains. Both IFN-α2a and antiserum inhibited the replication of CVA4 and increased the survival rates of neonatal mice during the early stages of infection. This neonatal murine model of CVA4 infection will be useful for the development of prophylactic and therapeutic vaccines and for screening of antiviral drugs targeting CVA4 to decrease morbidity and mortality. |
| first_indexed | 2024-03-08T21:58:58Z |
| format | Article |
| id | doaj.art-66dd93aa59514738b9e2d7dd21412196 |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-03-08T21:58:58Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-66dd93aa59514738b9e2d7dd214121962023-12-19T16:09:57ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512019-01-01811445145510.1080/22221751.2019.1673135A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugsZhenjie Zhang0Xingcheng Zhang1Michael J. Carr2Hong Zhou3Juan Li4Shaoqiong Liu5Tao Liu6Weijia Xing7Weifeng Shi8Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, People’s Republic of ChinaKey Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, People’s Republic of ChinaNational Virus Reference Laboratory, School of Medicine, University College Dublin, Dublin, IrelandKey Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, People’s Republic of ChinaKey Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, People’s Republic of ChinaKey Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, People’s Republic of ChinaDepartment of Obstetrics and Gynecology, Central Hospital of Taian, Taian, People’s Republic of ChinaSchool of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, People’s Republic of ChinaKey Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, People’s Republic of ChinaABSTRACTCoxsackievirus A4 (CVA4) infection can cause hand, foot and mouth disease (HFMD), an epidemic illness affecting neonatal and paediatric cohorts, which can develop to severe neurological disease with high mortality. In this study, we established the first ICR mouse model of CVA4 infection for the evaluation of inactivated vaccines and antiviral drug screening. The CVA4 YT226R strain was selected to infect the neonatal mice and three infectious factors were optimized to establish the infection model. The 3-day-old neonatal mice exhibited clinical symptoms such as hind limb paralysis and death. The severe inflammatory reactions were closely related to the abnormal expression of the acute phase response proinflammatory cytokine IL-6 and an imbalance in the IFN-γ/IL-4 ratio. Importantly, the inactivated CVA4 whole-virus vaccine induced humoral immune responses in adult females and the maternal antibodies afforded mice complete protection against lethal dose challenges of homologous or heterologous CVA4 strains. Both IFN-α2a and antiserum inhibited the replication of CVA4 and increased the survival rates of neonatal mice during the early stages of infection. This neonatal murine model of CVA4 infection will be useful for the development of prophylactic and therapeutic vaccines and for screening of antiviral drugs targeting CVA4 to decrease morbidity and mortality.https://www.tandfonline.com/doi/10.1080/22221751.2019.1673135HFMDcoxsackievirus A4murine modelinactivated vaccineantiviral drugs |
| spellingShingle | Zhenjie Zhang Xingcheng Zhang Michael J. Carr Hong Zhou Juan Li Shaoqiong Liu Tao Liu Weijia Xing Weifeng Shi A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs Emerging Microbes and Infections HFMD coxsackievirus A4 murine model inactivated vaccine antiviral drugs |
| title | A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs |
| title_full | A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs |
| title_fullStr | A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs |
| title_full_unstemmed | A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs |
| title_short | A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs |
| title_sort | neonatal murine model of coxsackievirus a4 infection for evaluation of vaccines and antiviral drugs |
| topic | HFMD coxsackievirus A4 murine model inactivated vaccine antiviral drugs |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2019.1673135 |
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