Mapping Attenuation Determinants in Enterovirus-D68

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2020 Aug 14

PMID 32784424

Citations 5

Authors

Ming Te Yeh

Sara Capponi

Adam Catching

Simone Bianco

Raul Andino

Affiliations

Soon will be listed here.

Abstract

Enterovirus (EV)-D68 has been associated with epidemics in the United Sates in 2014, 2016 and 2018. This study aims to identify potential viral virulence determinants. We found that neonatal type I interferon receptor knockout mice are susceptible to EV-D68 infection via intraperitoneal inoculation and were able to recapitulate the paralysis process observed in human disease. Among the EV-D68 strains tested, strain US/MO-14-18949 caused no observable disease in this mouse model, whereas the other strains caused paralysis and death. Sequence analysis revealed several conserved genetic changes among these virus strains: nucleotide positions 107 and 648 in the 5'-untranslated region (UTR); amino acid position 88 in VP3; 1, 148, 282 and 283 in VP1; 22 in 2A; 47 in 3A. A series of chimeric and point-mutated infectious clones were constructed to identify viral elements responsible for the distinct virulence. A single amino acid change from isoleucine to valine at position 88 in VP3 attenuated neurovirulence by reducing virus replication in the brain and spinal cord of infected mice.

Citing Articles

Enterovirus D68 infection in cotton rats results in systemic inflammation with detectable viremia associated with extracellular vesicle and neurologic disease.

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Structure and dynamics of enterovirus genotype networks.

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VP1 is the primary determinant of neuropathogenesis in a mouse model of enterovirus D68 acute flaccid myelitis.

Leser J, Frost J, Wilson C, Rudy M, Clarke P, Tyler K J Virol. 2024; 98(7):e0039724.

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Contemporary enterovirus-D68 isolates infect human spinal cord organoids.

Aguglia G, Coyne C, Dermody T, Williams J, Freeman M mBio. 2023; 14(4):e0105823.

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RNA Structure in the 5' Untranslated Region of Enterovirus D68 Strains with Differing Neurovirulence Phenotypes.

Eastman C, Tapprich W Viruses. 2023; 15(2).

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