Mutations in VP1 and 5′-UTR affect enterovirus 71 virulence

Ching Kun Chang, Shang Rung Wu, Ying Chin Chen, Kuen Jin Lee, Nai Hsiang Chung, Yi Ju Lu, Shu Ling Yu, Chia Chyi Liu, Yen Hung Chow

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Enterovirus 71 (EV71) is a major cause of hand, foot and mouth disease (HFMD). The current EV71 propagating in Vero (EV-V) or sub-passaged in RD (EV-R) cells was used as a pathogen. Interestingly, EV-R exhibited differential virulence; challenging human scavenger receptor class B2-expressing (hSCARB2-Tg) mice with EV71 revealed that EV-V was more virulent than EV-R: 100% of mice that received lethal amounts of EV-V died, while all the mice that received EV-R survived. Severe pathogenesis correlated with viral burdens and proinflammatory cytokine levels were observed in EV-V-challenged mice, but controversy in EV-R-challenged mice. Consensus sequence analysis revealed EV-R rapidly acquired complete mutations at E145G and S241L and partial mutations at V146I of VP1, and acquired a T to C substitution at nucleotide 494 of the 5′-UTR. EV-R exhibited higher binding affinity for another EV71 receptor, human P-selectin glycoprotein ligand-1 (hPSGL-1), than EV-V. Both EV71s exhibited no significant difference in binding to hSCARB2. The molecular modelling indicate that these mutations might influence EV71 engagement with PSGL-1 and in vivo virulence.

Original languageEnglish
Article number6688
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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Enterovirus
5' Untranslated Regions
Virulence
Mutation
Human Enterovirus A
Hand, Foot and Mouth Disease
Scavenger Receptors
Consensus Sequence
Viral Load
Sequence Analysis
Nucleotides
Cytokines

All Science Journal Classification (ASJC) codes

  • General

Cite this

Chang, C. K., Wu, S. R., Chen, Y. C., Lee, K. J., Chung, N. H., Lu, Y. J., ... Chow, Y. H. (2018). Mutations in VP1 and 5′-UTR affect enterovirus 71 virulence. Scientific reports, 8(1), [6688]. https://doi.org/10.1038/s41598-018-25091-7
Chang, Ching Kun ; Wu, Shang Rung ; Chen, Ying Chin ; Lee, Kuen Jin ; Chung, Nai Hsiang ; Lu, Yi Ju ; Yu, Shu Ling ; Liu, Chia Chyi ; Chow, Yen Hung. / Mutations in VP1 and 5′-UTR affect enterovirus 71 virulence. In: Scientific reports. 2018 ; Vol. 8, No. 1.
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abstract = "Enterovirus 71 (EV71) is a major cause of hand, foot and mouth disease (HFMD). The current EV71 propagating in Vero (EV-V) or sub-passaged in RD (EV-R) cells was used as a pathogen. Interestingly, EV-R exhibited differential virulence; challenging human scavenger receptor class B2-expressing (hSCARB2-Tg) mice with EV71 revealed that EV-V was more virulent than EV-R: 100{\%} of mice that received lethal amounts of EV-V died, while all the mice that received EV-R survived. Severe pathogenesis correlated with viral burdens and proinflammatory cytokine levels were observed in EV-V-challenged mice, but controversy in EV-R-challenged mice. Consensus sequence analysis revealed EV-R rapidly acquired complete mutations at E145G and S241L and partial mutations at V146I of VP1, and acquired a T to C substitution at nucleotide 494 of the 5′-UTR. EV-R exhibited higher binding affinity for another EV71 receptor, human P-selectin glycoprotein ligand-1 (hPSGL-1), than EV-V. Both EV71s exhibited no significant difference in binding to hSCARB2. The molecular modelling indicate that these mutations might influence EV71 engagement with PSGL-1 and in vivo virulence.",
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Chang, CK, Wu, SR, Chen, YC, Lee, KJ, Chung, NH, Lu, YJ, Yu, SL, Liu, CC & Chow, YH 2018, 'Mutations in VP1 and 5′-UTR affect enterovirus 71 virulence', Scientific reports, vol. 8, no. 1, 6688. https://doi.org/10.1038/s41598-018-25091-7

Mutations in VP1 and 5′-UTR affect enterovirus 71 virulence. / Chang, Ching Kun; Wu, Shang Rung; Chen, Ying Chin; Lee, Kuen Jin; Chung, Nai Hsiang; Lu, Yi Ju; Yu, Shu Ling; Liu, Chia Chyi; Chow, Yen Hung.

In: Scientific reports, Vol. 8, No. 1, 6688, 01.12.2018.

Research output: Contribution to journalArticle

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AU - Chang, Ching Kun

AU - Wu, Shang Rung

AU - Chen, Ying Chin

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AU - Chung, Nai Hsiang

AU - Lu, Yi Ju

AU - Yu, Shu Ling

AU - Liu, Chia Chyi

AU - Chow, Yen Hung

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