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Sequence duplication in 3' UTR modulates virus replication and virulence of Japanese encephalitis virus.

ABSTRACT: Japanese encephalitis virus (JEV), an important neurotropic pathogen, belongs to the genus Flavivirus of the family Flaviviridae and has caused huge threat to public health. It is still obscure regarding the functions of stem-loop (SL) and dumbbell (DB) domains of JEV 3' UTR in viral replication and virulence. In the current study, using the infectious clone of JEV SA14 strain as a backbone, we constructed a series of deletion mutants of 3' UTR to investigate their effects on virus replication. The results showed that partial deletions within SL or DB domain had no apparent effects on virus replication in both mammalian (BHK-21) and mosquito (C6/36) cells, suggesting that they were not involved in viral host-specific replication. However, the entire SL domain deletion (ΔVR) significantly reduced virus replication in both cell lines, indicating the important role of the complete SL domain in virus replication. The revertant of ΔVR mutant virus was obtained by serial passage in BHK-21 cells that acquired a duplication of DB domain (DB-dup) in the 3' UTR, which greatly restored virus replication as well as the capability to produce the subgenomic flavivirus RNAs (sfRNAs). Interestingly, the DB-dup mutant virus was highly attenuated in C57BL/6 mice despite replicating similar to WT JEV. These findings demonstrate the significant roles of the duplicated structures in 3' UTR in JEV replication and provide a novel strategy for the design of live-attenuated vaccines.

SUBMITTER: Zhang QY

PROVIDER: S-EPMC8725919 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Sequence duplication in 3' UTR modulates virus replication and virulence of Japanese encephalitis virus.

Zhang Qiu-Yan QY Liu Si-Qing SQ Li Xiao-Dan XD Li Jia-Qi JQ Zhang Ya-Nan YN Deng Cheng-Lin CL Zhang Hong-Lei HL Li Xu-Fang XF Fang Chun-Xiao CX Yang Feng-Xia FX Zhang Bo B Xu Yi Y Ye Han-Qing HQ

Emerging microbes & infections 20221201 1

Japanese encephalitis virus (JEV), an important neurotropic pathogen, belongs to the genus <i>Flavivirus</i> of the family <i>Flaviviridae</i> and has caused huge threat to public health. It is still obscure regarding the functions of stem-loop (SL) and dumbbell (DB) domains of JEV 3' UTR in viral replication and virulence. In the current study, using the infectious clone of JEV SA14 strain as a backbone, we constructed a series of deletion mutants of 3' UTR to investigate their effects on virus ...[more]

PMID: 34877923

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Dataset Information

Sequence duplication in 3' UTR modulates virus replication and virulence of Japanese encephalitis virus.

Publications

Sequence duplication in 3' UTR modulates virus replication and virulence of Japanese encephalitis virus.

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