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Viruses 2017, 9(1), 20; doi:10.3390/v9010020

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

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
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Michael Holbrook
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)
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Abstract

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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MDPI and ACS Style

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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