机构：[1]Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China[2] Department of Microbiology and Immunology, North Sichuan Medical College, Nanchong 637007, China [3]Department of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 100050, China[4] China National Biotech Group, Beijing 100029, China[5]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610000, China四川大学华西医院
The attenuated Japanese encephalitis virus (JEV) strain SA14-14-2 has been successfully utilized to prevent JEV infection; however, the attenuation determinants have not been fully elucidated. The envelope (E) protein of the attenuated JEV SA14-14-2 strain differs from that of the virulent parental SA14 strain at eight amino acid positions (E107, E138, E176, E177, E264, E279, E315, and E439). Here, we investigated the SA14-14-2-attenuation determinants by mutating E107, E138, E176, E177, and E279 in SA14-14-2 to their status in the parental virulent strain and tested the replication capacity, neurovirulence, neuroinvasiveness, and mortality associated with the mutated viruses in mice, as compared with those of JEV SA14-14-2 and SA14. Our findings indicated that revertant mutations at the E138 or E107 position significantly increased SA14-14-2 virulence, whereas other revertant mutations exhibited significant increases in neurovirulence only when combined with E138, E107, and other mutations. Revertant mutations at all eight positions in the E protein resulted in the highest degree of SA14-14-2 virulence, although this was still lower than that observed in SA14. These results demonstrated the critical role of the viral E protein in controlling JEV virulence and identified the amino acids at the E107 and E138 positions as the key determinants of SA14-14-2 neurovirulence.
基金：
the national key projects of “863” High Technology,
China (No. 2012AA02A401) and the Chinese Mega Project of Science Research for major new drug innovation
and developmental research for quality control of the JE live attenuated vaccine and polio vaccine (Grant No.
2014ZX09304316-003).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|3 区医学
小类|3 区病毒学
最新[2023]版：
大类|3 区医学
小类|3 区病毒学
第一作者：
第一作者机构：[1]Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China[2] Department of Microbiology and Immunology, North Sichuan Medical College, Nanchong 637007, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China[3]Department of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 100050, China[5]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610000, China
推荐引用方式(GB/T 7714)：
Jian Yang,Huiqiang Yang,Zhushi Li,et al.Envelope Protein Mutations L107F and E138K Are Important for Neurovirulence Attenuation for Japanese Encephalitis Virus SA14-14-2 Strain.[J].Viruses.2017,9(1):doi:10.3390/v9010020.
APA：
Jian Yang,Huiqiang Yang,Zhushi Li,Wei Wang,Hua Lin...&Yuhua Li.(2017).Envelope Protein Mutations L107F and E138K Are Important for Neurovirulence Attenuation for Japanese Encephalitis Virus SA14-14-2 Strain..Viruses,9,(1)
MLA：
Jian Yang,et al."Envelope Protein Mutations L107F and E138K Are Important for Neurovirulence Attenuation for Japanese Encephalitis Virus SA14-14-2 Strain.".Viruses 9..1(2017)
