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

Xu, Guanlun; Gao, Tingting; Wang, Zhijie; Zhang, Jun; Cui, Baoqiu; Shen, Xinxin; Zhou, Anyang; Zhang, Yuan; Zhao, Jie; Liu, Hong; Liang, Guangdong

doi:10.3390/v15030626

Cited by 6 publications

(14 citation statements)

References 55 publications

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“…In one of the last studies, Xu et al (2023) reported a JEV GI-GV substitution rate (95% HPD, 1.62×10 −4 –3.97×10 −4 ) comparable with our estimates. Notably, the sample size (115), clock model (UCLD) and tree prior (Bayesian Skyline) applied in the work of Xu et al (2023) were similar to two previously discussed studies with significantly lower JEV substitution rates (Pan et al, 2011; Gao et al, 2015). The possible explanation is that Xu et al (2023) provide new JEV nucleotide sequences, however without testing at least the measure of clock-like evolution by RTT, the question about the true factor of distorted inference of substitution rate persists unresolved.…”

Section: Resultssupporting

confidence: 91%

“…Despite the relatively large number of complete ORF sequences used in our study, the uncertainty in the assessment of the evolutionary timescale of the entire tree spans a large time interval (95% HPD of root height, 407–2333 years). A little more accurate estimates of time to MRCA of JEV GI-GV (95% HPD, 463–2100 years) were reported by Xu et al (2023) with a sample size of 115 complete genome sequences. In the other studies with smaller sample sizes, 95% HPD intervals for tree roots were much wider: Gao et al (2015) conclude that the MRCA of JEV GI-GV is estimated to have occurred 3255 years ago (95% HPD, 978–6125 years); Pan et al (2011) studied JEV GI-GIV defined the MRCA age of the entire clade as 1695 years ago (95% HPD, 548–3153 years).…”

Section: Resultsmentioning

confidence: 93%

“…The JEV genome consists of single-stranded positive-sense RNA with a length of about 10,965 nucleotides (nt). The genome encompasses a 10,245 nt single open reading frame (ORF), encoding a polyprotein, which includes three structural proteins: capsid (C), prosecutor membrane (prM) and envelope (E) proteins, and seven non-structural ones: NS1, NS2a, NS2b, NS3, N4a, NS4b, NS5 (Xu et al, 2023), (Lindenbach, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Reliable estimates of Japanese encephalitis virus evolutionary rate supported by a formal test of temporal signal

Ukraintceva,

Bondaryuk,

Sakhabeev

2024

Preprint

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Japanese encephalitis virus (JEV) is a positive-strand RNA virus causing encephalitis in humans, which is highly spread in East and Southeast Asia, Western Pacific countries and Australia. The main vector of JEV is Culex spp. (mainly C. tritaeniorhynchus). The intraspecies structure of JEV comprises five genotypes (GI-GV). In the previous studies, the substitution rate and the age of the JEV most recent common ancestor (MRCA) based on complete open reading frame (ORF) / whole genome sequences were reported, however, the estimates are significantly different between some of the studies. Most importantly, the temporal signal in nucleotide data as the key aspect of the molecular clock application was evaluated by neither formal nor informal tests. In February 2023, we found 325 non-recombinant nucleotide sequences of ORF with known collection dates. The purpose of our study is the evaluation of temporal signal in the JEV ORF nucleotide data set using the Bayesian approach with the subsequent re-estimation of substitution rate and the age of the JEV common clade (GI-GV) and two JEV genotypes (GI and GIII) characterized by the number of sequences enough for reliable estimates. Results showed the presence of temporal signal in all analyzed data set. The substitution rate of the JEV GI-GV was 2.41×10^−4 (95% highest posterior density (HPD) interval, 1.67×10^−4—3.14×10^−4) or approximately 2.5 nucleotide substitutions per ORF (10,245 nucleotides) per year that is one the lowest substitution rate among the species closely related to JEV and other well-studied members of mosquito-borne flaviviruses. The substitution rate of GI and GIII evaluated as 4.13×10^−4 (95% HPD interval, 3.45×10^−4—4.82×10^−4) and 6.17×10^−5 (95% HPD interval 3.84×10^−5—8.62×10^−5), accordingly, with the ages of clades of 153 (95% HPD, 87—237) and 216 (95% HPD, 139—317), respectively. The root height of JEV is 1234 years (95% HPD, 407—2333). To the best of our knowledge, this study provides the first reliable substitution rate assessment of the global clade of JEV embracing all five genotypes.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Reliable estimates of Japanese encephalitis virus evolutionary rate supported by a formal test of temporal signal

Ukraintceva,

Bondaryuk,

Sakhabeev

2024

Preprint

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“…These aspects are relevant and require further investigations considering that during the recent outbreak of JEV in Australia in 2021/2022 over 80 piggeries were affected [73]. Interestingly, this outbreak was caused by a recently emerged genotype IV virus [74], which had a high mutation rate, possibly enabling a fast virus evolution and adaptation [75]. To our knowledge it is not known whether direct transmission events between pigs took place in Australia and whether the characteristics of the virus changed during the epidemic.…”

Section: Discussionmentioning

confidence: 99%

Fitness adaptations of Japanese encephalitis virus in pigs following vector-free serial passaging

Marti,

Nater,

Magalhaes

et al. 2024

Preprint

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Japanese encephalitis virus (JEV) is a zoonotic mosquito-transmitted Flavivirus circulating in birds and pigs. In humans, JEV can cause severe viral encephalitis with high mortality. Considering that vector-free direct virus transmission was observed in pigs, JEV introduction into an immunologically naïve pig population could result in a series of direct transmissions disrupting the alternating host cycling between vertebrates and mosquitoes. To assess the potential consequences of such a realistic scenario, we passaged JEV ten times in pigs. This resulted in higherin vivoviral replication, increased shedding, and stronger innate immune responses in pigs. Nevertheless, the viral tissue tropism remained similar and frequency of direct transmission was not enhanced. Next generation sequencing showed single nucleotide deviations in 10% of the genome during passaging. In total, 25 point mutations were selected to reach a frequency of at least 35% in one of the passages. From these, six mutations resulted in amino acid changes located in the precursor of membrane, the envelope, the non-structural 3 and the non-structural 5 proteins. In a competition experiment with two lines of passaging, the mutation M374L in the envelope protein and N275D in the non-structural protein 5 showed a fitness advantage in pigs. Altogether, the interruption of the alternating host cycle of JEV caused a prominent selection of viral quasispecies as well as selection of de novo mutations associated with fitness gains in pigs, albeit without enhancing direct transmission frequency.Author summaryJapanese encephalitis virus (JEV) represents a major health threat in parts of Asia and Oceania. Primary vertebrate hosts are birds and pigs, but human infection also occurs and can cause severe encephalitis with high mortality. Like other Flaviviruses transmitted by insect bites, JEV requires replication in alternating cycles between mosquitoes on one side and birds or pigs on the other side. However, we previously reported that direct transmissions between pigs in absence of mosquitos can occur. Considering the increased risks for such events after the spread of JEV to a new region with immunologically naïve pigs, the present study was performed to understand if and how a series of direct transmissions would promote JEV adaptations to pigs and change virus-host interactions. Pigs infected with JEV passaged ten times showed enhanced clinical symptoms and stronger antiviral immune response, but luckily no increase in direct transmission was observed. Nevertheless, genomic analysis demonstrated a complete change in dominant virus variants, as well as selection of six viral amino acid changes. This indicates that interruptions of the alternating lifestyle of JEV causes a strong evolutionary pressure, which through fitness adaptations can change the viral characteristics.

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“…The genotype of JEV currently circulating in Australia was detected in the Tiwi Islands, Northern Territory (NT), in February 2021, and one year later in other states of Australia (Sikazwe et al, 2022). However, it is estimated that the Australian clade emerged six years ago, suggesting that this clade of GIV viruses had been cryptically circulating in Australia for several years (95% HPD, 2–14) (Xu et al, 2023). There were 45 human cases of this vaccine-preventable disease recorded during 2022, including seven deaths.…”

Section: Introductionmentioning

confidence: 99%

Long-term co-circulation of multiple arboviruses in southeast Australia revealed by xeno-monitoring and metatranscriptomics

Julia S. P. Vieira,

Onn,

Shivas

et al. 2024

Preprint

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Arbovirus surveillance of wild-caught mosquitoes is an affordable and sensitive means of monitoring virus transmission dynamics at various spatial-temporal scales, and emergence and re-emergence during epidemic and interepidemic periods. A variety of molecular diagnostics for arbovirus screening of mosquitoes (known as xeno-monitoring) are available, but most provide limited information about virus diversity. PCR-based screening coupled with metatranscriptomics is an increasingly affordable and sensitive pipeline for integrating complete viral genome sequencing into surveillance programs. This enables large-scale, high-throughput arbovirus screening from diverse samples. We collected mosquitoes in CO2-baited light traps from five urban parks in Brisbane from March 2021 to May 2022. Mosquito pools of ≤200 specimens were screened for alphaviruses and orthoflaviviruses using virus genus-specific primers and reverse transcription quantitative PCR (qRT-PCR). A subset of virus-positive samples was then processed using a mosquito-specific ribosomal RNA depletion method and then sequenced on the Illumina NextSeq. Overall, 54,670 mosquitoes, representing 26 species were screened in 382 pools. Thirty detections of arboviruses were made in 28 pools. Twenty of these positive pools were further characterised using meta-transcriptomics generating 18 full-length genomes. These full-length sequences belonged to four medically relevant arboviruses: Barmah Forest, Ross River, Sindbis-like and Stratford viruses. Phylogenetic and evolutionary analyses revealed the evolutionary progression of arbovirus lineages over the last 100 years, highlighting long-distance dispersal across the Australian continent and continuous circulation characterised by constant turnover of virus lineages.

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

Cited by 6 publications

References 55 publications

Reliable estimates of Japanese encephalitis virus evolutionary rate supported by a formal test of temporal signal

Reliable estimates of Japanese encephalitis virus evolutionary rate supported by a formal test of temporal signal

Fitness adaptations of Japanese encephalitis virus in pigs following vector-free serial passaging

Long-term co-circulation of multiple arboviruses in southeast Australia revealed by xeno-monitoring and metatranscriptomics

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