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. 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

Yi Xu  1 , Shuzhi Ma  2 , Limeng Zhu  3 , Zhiqiu Huang  4 , Liyun Chen  4 , Yuhua Xu  2 , Haibin Yin  4 , Tao Peng  5 , Yi Wang  6
Affiliations

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

Yi Xu et al. Antiviral Res. 2017 Jan.

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.

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