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
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:
national key projects of "863" High Technology, China [2012AA02A401]; Chinese Mega Project of Science Research [2014ZX09304316-003]
语种:
外文
WOS:
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-BASEL.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-BASEL,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-BASEL 9..1(2017):-