The 5′ and 3′ Untranslated Regions of the Japanese Encephalitis Virus (JEV): Molecular Genetics and Higher Order Structures

Liu, Hong; Zhang, Jun; Niu, Yuzhen; Liang, Guodong

doi:10.3389/fmicb.2021.730045

Cited by 10 publications

(14 citation statements)

References 60 publications

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“…Our previous study [ 5 ] identified that a 300 nt-length region located at the beginning of the JEV 3’UTR, termed variable region (VR), exhibited significant genotypic specificity. In this study, the VR region of the 115 JEV sequences was also analyzed to verify whether the genomic sequences of the emerging JEV GIV conform to the phylogenetic characteristics of the JEV population.…”

Section: Methodsmentioning

confidence: 99%

“…The genome length of JEV is about 10,965 nt and contains a single open reading frame (ORF) encoding a polyprotein that is processed into three structural (C, M, and E) and seven nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins [ 3 , 4 ]. The 5′ and 3’ untranslated regions (UTR) are located on both sides of the ORF and contain abundant cis-acting elements that are crucial for virus replication, immunity, and pathogenicity [ 5 ]. Previous studies have indicated three domains in E protein, and the E protein domain III, which has the main cites for neutralizing antibodies, is considered to play a key role in activating receptor and membrane fusion [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Re-Emerged Genotype IV of Japanese Encephalitis Virus Is the Youngest Virus in Evolution

Gao

Wang

et al. 2023

Viruses

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An outbreak of viral encephalitis caused by a Japanese encephalitis virus (JEV) genotype IV infection occurred in Australia between 2021 and 2022. A total of 47 cases and seven deaths were reported as of November 2022. This is the first outbreak of human viral encephalitis caused by JEV GIV since it was first isolated in Indonesia in the late 1970s. Here, a comprehensive phylogenetic analysis based on the whole genome sequences of JEVs revealed it emerged 1037 years ago (95% HPD: 463 to 2100 years). The evolutionary order of JEV genotypes is as follows: GV, GIII, GII, GI, and GIV. The JEV GIV emerged 122 years ago (95% HPD: 57–233) and is the youngest viral lineage. The mean substitution rate of the JEV GIV lineage was 1.145 × 10−3 (95% HPD values, 9.55 × 10−4, 1.35 × 10−3), belonging to rapidly evolving viruses. A series of amino acid mutations with the changes of physico-chemical properties located in the functional important domains within the core and E proteins distinguished emerging GIV isolates from old ones. These results demonstrate the JEV GIV is the youngest JEV genotype at a rapid evolution stage and has good host/vector adaptability for introduction to non-endemic areas. Thus, surveillance of JEVs is highly recommended.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Re-Emerged Genotype IV of Japanese Encephalitis Virus Is the Youngest Virus in Evolution

Gao

Wang

et al. 2023

Viruses

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“…JEV has a single-stranded RNA genome that contains only an open reading frame (ORF) flanked by the 5’ and 3’ untranslated regions [ 4 ]. The ORF encodes three structural proteins [capsid (C), pre-membrane (prM), and envelope (E) proteins] and seven non-structural (NS) proteins (NS1, NS2a, NS2b, NS3, NS4a, NS4b, and NS5) [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Tracing the spatiotemporal phylodynamics of Japanese encephalitis virus genotype I throughout Asia and the western Pacific

Feng

Wang

et al. 2023

PLoS Negl Trop Dis

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Background Japanese encephalitis virus (JEV; Flaviridae: Flavivirus) causes Japanese encephalitis (JE), which is the most important arboviral disease in Asia and the western Pacific. Among the five JEV genotypes (GI–IV), GI has dominated traditional epidemic regions in the past 20 years. We investigated the transmission dynamics of JEV GI through genetic analyses. Methods We generated 18 JEV GI near full length sequences by using multiple sequencing approaches from mosquitoes collected in natural settings or from viral isolates obtained through cell culture. We performed phylogenetic and molecular clock analyses to reconstruct the evolutionary history by integrating our data with 113 publicly available JEV GI sequences. Results We identified two subtypes of JEV GI (GIa and GIb), with a rate of 5.94 × 10−4 substitutions per site per year (s/s/y). At present, GIa still circulates within a limited region, exhibited no significant growth, the newest strain was discovered in China (Yunnan) in 2017, whereas most JEV strains circulating belong to the GIb clade. During the past 30 years, two large GIb clades have triggered epidemics in eastern Asia: one epidemic occurred in 1992 [95% highest posterior density (HPD) = 1989–1995] and the causative strain circulates mainly in southern China (Yunnan, Shanghai, Guangdong, and Taiwan) (Clade 1); the other epidemic occurred in 1997 (95% HPD = 1994–1999) and the causative strain has increased in circulation in northern and southern China during the past 5 years (Clade 2). An emerging variant of Clade 2 contains two new amino acid markers (NS2a-151V, NS4-169K) that emerged around 2005; this variant has demonstrated exponential growth in northern China. Conclusion JEV GI stain circulating in Asia have shifted during the past 30 years, spatiotemporal differences were observed among JEV GI subclade. GIa is still circulating within a limited range, exhibite no significant growth. Two large GIb clades have triggered epidemics in eastern Asia, all JEV sequences identified in northern China during the past 5 years were of the new emerging variant of G1b-clade 2.

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“…To date, to our knowledge, two studies have utilized unbiased techniques to examine the CSF proteome in human patients with confirmed JEV infection; while they demonstrate the feasibility of the methods, the patients were not confirmed by seroneutralization and included relatively small numbers of patients (10 and 26 JE patients). , There have been a handful of studies utilizing ELISA methods to target specific proteins; however, these rarely used power calculations in their experimental design, nor did they include adequate controls. − Analysis of the transcriptome and proteome in animal models − and cell culture ,,− have been performed; however, the comparability to human CSF and comparison with other neurological infections is limited. Furthermore, mRNA expression does not directly correlate with that of the corresponding protein …”

Section: Discussionmentioning

confidence: 99%

Deep Proteomics Network and Machine Learning Analysis of Human Cerebrospinal Fluid in Japanese Encephalitis Virus Infection

et al. 2023

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Japanese encephalitis virus is a leading cause of neurological infection in the Asia-Pacific region with no means of detection in more remote areas. We aimed to test the hypothesis of a Japanese encephalitis (JE) protein signature in human cerebrospinal fluid (CSF) that could be harnessed in a rapid diagnostic test (RDT), contribute to understanding the host response and predict outcome during infection. Liquid chromatography and tandem mass spectrometry (LC−MS/MS), using extensive offline fractionation and tandem mass tag labeling (TMT), enabled comparison of the deep CSF proteome in JE vs other confirmed neurological infections (non-JE). Verification was performed using data-independent acquisition (DIA) LC−MS/MS. 5,070 proteins were identified, including 4,805 human proteins and 265 pathogen proteins. Feature selection and predictive modeling using TMT analysis of 147 patient samples enabled the development of a nine-protein JE diagnostic signature. This was tested using DIA analysis of an independent group of 16 patient samples, demonstrating 82% accuracy. Ultimately, validation in a larger group of patients and different locations could help refine the list to 2−3 proteins for an RDT. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD034789 and 10.6019/PXD034789.

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The 5′ and 3′ Untranslated Regions of the Japanese Encephalitis Virus (JEV): Molecular Genetics and Higher Order Structures

Cited by 10 publications

References 60 publications

Re-Emerged Genotype IV of Japanese Encephalitis Virus Is the Youngest Virus in Evolution

Re-Emerged Genotype IV of Japanese Encephalitis Virus Is the Youngest Virus in Evolution

Tracing the spatiotemporal phylodynamics of Japanese encephalitis virus genotype I throughout Asia and the western Pacific

Deep Proteomics Network and Machine Learning Analysis of Human Cerebrospinal Fluid in Japanese Encephalitis Virus Infection

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