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Antiviral Res. 2017 Jan;137:67-75. doi: 10.1016/j.antiviral.2016.11.008. Epub 2016 Nov 15.

Clinically isolated enterovirus A71 subgenogroup C4 strain with lethal pathogenicity in 14-day-old mice and the application as an EV-A71 mouse infection model.

Author information

1
Guangzhou Women and Children's Medical Center, Guangzhou Medical University Guangzhou, China.
2
Guangdong South China United Vaccine Institute, Guangzhou, China; Sino-French Hoffmann Institute of Immunology, State Key Laboratory of Respiratory Disease, College of Basic Medical Science, Guangzhou Medical University, Guangzhou, China.
3
Sino-French Hoffmann Institute of Immunology, State Key Laboratory of Respiratory Disease, College of Basic Medical Science, Guangzhou Medical University, Guangzhou, China.
4
Guangdong South China United Vaccine Institute, Guangzhou, China.
5
Guangdong South China United Vaccine Institute, Guangzhou, China; Sino-French Hoffmann Institute of Immunology, State Key Laboratory of Respiratory Disease, College of Basic Medical Science, Guangzhou Medical University, Guangzhou, China. Electronic address: peng_tao@gibh.ac.cn.
6
Guangdong South China United Vaccine Institute, Guangzhou, China; The First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou, China. Electronic address: wang_yi79@hotmail.com.

Abstract

The Enterovirus A71 (EV-A71) subgenogroup C4 is prevalent in China. EV-A71 causes hand, foot and mouth disease (HFMD) in children and may lead to severe neurological diseases. The development of antiviral and protective vaccines against EV-A71 is significantly hindered by the lack of suitable animal models to recapitulate human neurological symptoms. In this study, GZ-CII, a highly virulent EV-A71 subgenogroup C4 strain, was isolated from hospitalized children with HFMD. Intraperitoneal infections of GZ-CII resulted in progressive neurological disease in mice as old as 14 days. Administration of an inactivated EV-A71 vaccine or an anti-EV-A71 immune serum protected the mice against the GZ-CII infection. This demonstrated that a mouse model with EV-A71 GZ-CII could be used to evaluate potential vaccine candidates and therapeutics for subgenogroup C4. Comparing the genome sequence of GZ-CII with that of the avirulent EV-A71 subgenogroup C4 strain revealed unique mutations in GZ-CII. When mutation VP2-K149I was introduced into the nonpathogenic EV-A71 subgenogroup C4 strain, the variant similar to GZ-CII significantly increased viral replication and virulence in mice. These results indicated that the VP2-K149I mutation played an important role in enhancing the virulence of the EV-A71 subgenogroup C4 strain in mice, and that mice infected with the GZ-CII strain are a promising model for evaluating vaccines and therapeutics against the EV-A71 subgenogroup C4.

KEYWORDS:

Enterovirus A71 (EV-A71); Mouse infection model; Primary isolate; Vaccine

PMID:
27864074
DOI:
10.1016/j.antiviral.2016.11.008
[Indexed for MEDLINE]

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