Zika Virus Fatally Infects Wild Type Neonatal Mice and Replicates in Central Nervous System
Shuxuan Li,
Najealicka Armstrong,
Huan Zhao,
Wangheng Hou,
Jian Liu,
Chunye Chen,
Junkai Wan,
Wei Wang,
Chunlian Zhong,
Che Liu,
Hua Zhu,
Ningshao Xia,
Tong Cheng,
Qiyi Tang
Affiliations
Shuxuan Li
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China
Najealicka Armstrong
Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA
Huan Zhao
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China
Wangheng Hou
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China
Jian Liu
Department of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers University, 225 Warren Street, Newark, NJ 070101, USA
Chunye Chen
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China
Junkai Wan
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China
Wei Wang
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China
Chunlian Zhong
Department of Basic Medical Sciences, Medical College of Xiamen University, Xiamen 361102, China
Che Liu
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China
Hua Zhu
Department of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers University, 225 Warren Street, Newark, NJ 070101, USA
Ningshao Xia
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China
Tong Cheng
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China
Qiyi Tang
Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA
Zika virus (ZIKV) has been defined as a teratogenic pathogen behind the increased number of cases of microcephaly in French Polynesia, Brazil, Puerto Rico, and other South American countries. Experimental studies using animal models have achieved tremendous insight into understanding the viral pathogenesis, transmission, teratogenic mechanisms, and virus–host interactions. However, the animals used in published investigations are mostly interferon (IFN)-compromised, either genetically or via antibody treatment. Herein, we studied ZIKV infection in IFN-competent mice using African (MR766) and Asian strains (PRVABC59 and SZ-WIV01). After testing four different species of mice, we found that BALB/c neonatal mice were resistant to ZIKV infection, that Kunming, ICR and C57BL/6 neonatal mice were fatally susceptible to ZIKV infection, and that the fatality of C57BL/6 neonates from 1 to 3 days old were in a viral dose-dependent manner. The size and weight of the brain were significantly reduced, and the ZIKV-infected mice showed neuronal symptoms such as hind-limb paralysis, tremor, and poor balance during walking. Pathologic and immunofluorescent experiments revealed that ZIKV infected different areas of the central nervous system (CNS) including gray matter, hippocampus, cerebral cortex, and spinal cord, but not olfactory bulb. Interestingly, ZIKV replicated in multiple organs and resulted in pathogenesis in liver and testis, implying that ZIKV infection may engender a high health risk in neonates by postnatal infection. In summary, we investigated ZIKV pathogenesis using an animal model that is not IFN-compromised.
