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

Yang, Jian Ying; Yang, Haijun; Li, Zhushi; Wang, Wei; Lin, Hua; Liu, Lina; Ni, Qian‐Zhi; Liu, Xinyu; Zeng, Xianwu; Wu, Yonglin; Li, Yuhua

doi:10.3390/v9010020

Cited by 39 publications

(55 citation statements)

References 36 publications

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“…Currently, some articles have confirmed several significant amino acid residue mutations on E gene. For example, mutations at residues L107F, E138K, I176V, T177A, E244G, Q264H, K279M, A315V, S366A and K439R are essential and important for neurovirulence attenuation [ 52 ], especially L107F, E138K [ 53 ] and M279K [ 54 ]. Mutation at residue S123R increase pathogenicity [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Serological and molecular epidemiology of Japanese Encephalitis in Zhejiang, China, 2015-2018

Deng

Yan

et al. 2020

PLoS Negl Trop Dis

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Background Shifts have occurred in the epidemiological characteristics of Japanese encephalitis (JE), extending from the molecular level to the population level. The aim of this study was to investigate the seroprevalence of JE neutralizing antibodies in healthy populations from different age groups in Zhejiang Province, and to conduct mosquito monitoring to evaluate the infection rate of Japanese encephalitis virus (JEV) among vectors, as well as the molecular characteristics of the E gene of isolated JEV strains. Methodology/Principal findings A total of 1190 sera samples were screened by a microseroneutralization test, including 429 infants (28d-11m) and 761 participants (2y-82y). For those under 1 year old, the geometric mean titers (GMTs) of the JE neutralizing antibody was 9.49 at birth and significantly declined as the age of month increased (r =-0.225, P<0.001). For those above 1-year old, seropositive proportions were higher in subjects aged 1-3 years old as well as �25 years old (65%-75%), and relatively lower in subjects aged between 4-25 years old (22%-55%). Four or more years after the 2 nd dose of JEV-L (first dose administered at 8 months and the second at 2 years of age), the seropositive proportion decreased to 32.5%, and GMTs decreased to 8.08. A total of 87,201 mosquitoes were collected from livestock sheds in 6 surveillance sites during 2015-2018, from which 139 E gene sequences were successfully amplified. The annual infection rate according to bias-corrected maximum likelihood estimation of JEV in Culex tritaeniorhynchus was 1.56, 2.36, 5.65 and 1.77 per 1000, respectively. JEV strains isolated during 2015-2018 all belonged to Genotype I. The E gene of amplified 139 samples differed from the JEV-L vaccine strain at fourteen amino acid residues, including the eight key residues related to virulence and virus attenuation. No divergence was observed at the sites related to antigenicity. Conclusions/Significance Zhejiang Province was at a high risk of JE exposure due to relatively lower neutralizing antibody levels among the younger-aged population and higher infection rates of JEV in PLOS NEGLECTED TROPICAL DISEASES

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Section: Discussionmentioning

confidence: 99%

Serological and molecular epidemiology of Japanese Encephalitis in Zhejiang, China, 2015-2018

Deng

Yan

et al. 2020

PLoS Negl Trop Dis

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“…The chimeric virus JEV SA14/SA14-14-2, which took the JEV wild-type SA14 as the backbone, and in which only the prM/E genes of the JEV SA14 were replaced with that of JEV vaccine strain SA14-14-2, was recovered from BHK21 cells, and there are 10 amino acids substitution in the E protein of the chimera (L107F, E138K, I176T, V177A, E244G, Q264H, K279M, A315V, K439R, and G447D). We speculated that the characteristics of chimera should be similar with the vaccine strain from previous studies [20, 31]. In order to identify this, the biological characteristics of JEV SA14/SA14-14-2 were identified with the plaque assay and growth curve.…”

Section: Discussionmentioning

confidence: 99%

Chimeric Japanese Encephalitis Virus SA14/SA14-14-2 Was Virulence Attenuated and Protected the Challenge of Wild-Type Strain SA14

Ron

Leng

Feng

et al. 2019

Canadian Journal of Infectious Diseases and Medical Microbiolog

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The attenuated Japanese encephalitis virus (JEV) live vaccine SA14-14-2 prepared from wild-type (WT) strain SA14 was licensed to prevent Japanese encephalitis (JE) in 1989 in China. Many studies showed that the premembrane (prM) and envelope (E) protein were the crucial determinant of virulence and immunogenicity of JEV. So we are interested in whether the substitution of prM/E of JEV WT SA14 with those of vaccine strain SA14-14-2 could decrease neurovirulence and prevent the challenge of JEV WT SA14. Molecular clone technique was used to replace the prM/E gene of JEV WT strain SA14 with those of vaccine strain SA14-14-2 to construct the infectious clone of chimeric virus (designated JEV SA14/SA14-14-2), the chimeric virus recovered from BHK21 cells upon electrotransfection of RNA into BHK21 cells. The results showed that the recovered chimeric virus was highly attenuated in mice, and a single immunization elicited strong protective immunity in a dose-dependent manner. This study increases our understanding of the molecular mechanisms of neurovirulence attenuation and immunogenicity of JEV.

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“…53,[86][87][88] Further, revertant mutations at E107 and E138 of the E gene resulted in greater SA14-14-2 virulence. 89 With JEV, three substitutions in domain III 90 (305F → V, 326K → E, and 380R → T) showed that neither positions 380 (380T) nor 305 (305V) independently affected neuroinvasiveness, whereas residue 326 was found to be a critical determinant of YFV neuroinvasiveness. 91 The study also indicated that changes at position 303 may be important for YFV virulence.…”

Section: Mutations In the E Protein Genementioning

confidence: 99%

Research advancements in the neurological presentation of flaviviruses

Chen

Zhang

et al. 2018

Reviews in Medical Virology

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Summary Owing to the large‐scale epidemic of Zika virus disease and its association with microcephaly, properties that allow flaviviruses to cause nervous system diseases are an important area of investigation. At present, although potential pathogenic mechanisms of flaviviruses in the nervous system have been examined, they have not been completely elucidated. In this paper, we review the possible mechanisms of blood‐brain barrier penetration, the pathological effects on neurons, and the association between virus mutations and neurotoxicity. A hypothesis on neurotoxicity caused by the Zika virus is presented. Clarifying the mechanisms of virulence of flaviviruses will be helpful in finding better antiviral drugs and optimizing the treatment of symptoms.

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

Cited by 39 publications

References 36 publications

Serological and molecular epidemiology of Japanese Encephalitis in Zhejiang, China, 2015-2018

Serological and molecular epidemiology of Japanese Encephalitis in Zhejiang, China, 2015-2018

Chimeric Japanese Encephalitis Virus SA14/SA14-14-2 Was Virulence Attenuated and Protected the Challenge of Wild-Type Strain SA14

Research advancements in the neurological presentation of flaviviruses

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