Molecular Basis of Neurovirulence of Flury Rabies Virus Vaccine Strains: Importance of the Polymerase and the Glycoprotein R333Q Mutation

被引：40

作者：

Tao, Lihong ^{[1
,2
]}

Ge, Jinying ^{[1
,2
]}

Wang, Xijun ^{[1
,2
]}

Zhai, Hongyue ^{[1
,2
]}

Hua, Tao ^{[1
,2
]}

Zhao, Bolin ^{[1
,2
]}

Kong, Dongni ^{[1
,2
]}

Yang, Chinglai ^{[3
]}

Chen, Hualan ^{[1
,2
]}

Bu, Zhigao ^{[1
,2
]}

机构：

[1] CAAS, Harbin Vet Res Inst, Minist Agr, Vet Publ Hlth Lab, Harbin 150001, Peoples R China

[2] CAAS, Harbin Vet Res Inst, State Key Lab Vet Biotechnol, Harbin 150001, Peoples R China

[3] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA

来源：

JOURNAL OF VIROLOGY | 2010年 / 84卷 / 17期

关键词：

ADULT MICE; IMMUNE-RESPONSES; INFLUENZA-VIRUS; NERVOUS-SYSTEM; MATRIX PROTEIN; CLONED CDNA; APOPTOSIS; PATHOGENICITY; GENE; REPLICATION;

D O I：

10.1128/JVI.00787-10

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The molecular mechanisms associated with rabies virus (RV) virulence are not fully understood. In this study, the RV Flury low-egg-passage (LEP) and high-egg-passage (HEP) strains were used as models to explore the attenuation mechanism of RV. The results of our studies confirmed that the R333Q mutation in the glycoprotein (G(R333Q)) is crucial for the attenuation of Flury RV in mice. The R333Q mutation is stably maintained in the HEP genome background but not in the LEP genome background during replication in mouse brain tissue or cell culture. Further investigation using chimeric viruses revealed that the polymerase L gene determines the genetic stability of the G(R333Q) mutation during replication. Moreover, a recombinant RV containing the LEP G protein with the R333Q mutation and the HEP L gene showed significant attenuation, genetic stability, enhancement of apoptosis, and immunogenicity. These results indicate that attenuation of the RV Flury strain results from the coevolution of G and L elements and provide important information for the generation of safer and more effective modified live rabies vaccine.

引用

页码：8926 / 8936

页数：11