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Viruses. 2017 Jan 21;9(1). pii: E20. doi: 10.3390/v9010020.

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

Yang J1,2, Yang H3, Li Z4, Wang W5, Lin H6, Liu L7, Ni Q8, Liu X9, Zeng X10, Wu Y11, Li Y12,13,14.

Author information

1
Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China. jiany74@163.com.
2
Department of Microbiology and Immunology, North Sichuan Medical College, Nanchong 637007, China. jiany74@163.com.
3
Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China. yang-anan@163.com.
4
Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China. changdc123@sina.com.
5
Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China. suntina926@163.com.
6
Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China. scciqlh@126.com.
7
Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China. linaliu@163.com.
8
Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China. nqz1986@126.com.
9
Department of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 100050, China. xinyuliu@hotmail.com.
10
Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China. zengxw64@163.com.
11
China National Biotech Group, Beijing 100029, China. wuyonglin@sinopharm.com.
12
Department of Viral Vaccine, Chengdu Institute of Biological Products Co., Ltd., China National Biotech Group, Chengdu 610023, China. liyuhua@nifdc.org.cn.
13
Department of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 100050, China. liyuhua@nifdc.org.cn.
14
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610000, China. liyuhua@nifdc.org.cn.

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.

KEYWORDS:

Japanese encephalitis virus; SA14-14-2; attenuation mechanism; neuroinvasiveness; neurovirulence

PMID:
28117725
PMCID:
PMC5294989
DOI:
10.3390/v9010020
[Indexed for MEDLINE]
Free PMC Article

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