A single mutation in capsid protein VP1 (Q145E) of a genogroup C4 strain of human enterovirus 71 generates a mouse-virulent phenotype

被引：43

作者：

Zaini, Zainun ^{[1
]}

McMinn, Peter ^{[1
]}

机构：

[1] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia

来源：

JOURNAL OF GENERAL VIROLOGY | 2012年 / 93卷

关键词：

CENTRAL-NERVOUS-SYSTEM; CYNOMOLGUS MONKEYS; INFECTION; DISEASE; MODEL; MICE; ADAPTATION; GENOTYPE; VACCINE; VIRUS;

D O I：

10.1099/vir.0.043893-0

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

We modified the capsid protein Of a human enterovirus 71 (HEV71) belonging to subgenogroup C4 (HEV71-C4) to generate a mouse virulent strain, based on the genetic information derived from our previous subgenogroup B3 mouse-adapted virus. Infectious clone-derived mutant virus populations containing the capsid protein mutations VP1-Q145E and VP1-Q145G were generated by site-directed mutagenesis of an infectious clone of a subgenogroup C4 strain. Viruses expressing the VP1-Q145E were virulent in 5-day-old BALB/c mice with 100% mortality rate observed. Skeletal muscle appears to be the primary site of replication of this virus with limb muscle showing severe myositis. Virus was also isolated from spleen, liver, heart and brain of infected mice. This study demonstrates that introducing a key mutation into the HEV71 VP1 capsid protein is able to generate a mouse virulent HEV71 strain from a different genogroup as well as providing an alternative strategy for the generation of mouse virulent HEV71.

引用

页码：1935 / 1940

页数：6

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