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Envelope Protein Mutations L107F and E138K Are Important for Neurovirulence Attenuation for Japanese Encephalitis Virus SA14-14-2 Strain

Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China
Department of Microbiology and Immunology, North Sichuan Medical College, Nanchong 637007, China
Department of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 100050, China
China National Biotech Group, Beijing 100029, China
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610000, China
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Michael Holbrook
Viruses 2017, 9(1), 20;
Received: 31 October 2016 / Revised: 1 January 2017 / Accepted: 16 January 2017 / Published: 21 January 2017
(This article belongs to the Special Issue Advances in Flavivirus Research)
PDF [1413 KB, uploaded 21 January 2017]


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. View Full-Text
Keywords: attenuation mechanism; Japanese encephalitis virus; SA14-14-2; neuroinvasiveness; neurovirulence attenuation mechanism; Japanese encephalitis virus; SA14-14-2; neuroinvasiveness; neurovirulence

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Yang, J.; Yang, H.; Li, Z.; Wang, W.; Lin, H.; Liu, L.; Ni, Q.; Liu, X.; Zeng, X.; Wu, Y.; Li, Y. Envelope Protein Mutations L107F and E138K Are Important for Neurovirulence Attenuation for Japanese Encephalitis Virus SA14-14-2 Strain. Viruses 2017, 9, 20.

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