| Title: |
Mapping Attenuation Determinants in Enterovirus-D68 |
| Authors: |
Yeh, Ming Te; Capponi, Sara; Catching, Adam; Bianco, Simone; Andino, Raul |
| Source: |
Viruses, vol 12, iss 8 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2020 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
Microbiology; Biological Sciences; Neurosciences; Biodefense; Infectious Diseases; Genetics; Rare Diseases; Emerging Infectious Diseases; 2.1 Biological and endogenous factors; 2.2 Factors relating to the physical environment; Infection; Good Health and Well Being; 5' Untranslated Regions; Amino Acid Substitution; Animals; Brain; Capsid Proteins; Cell Line; Tumor; Disease Models; Animal; Enterovirus D; Human; Enterovirus Infections; Genes; Viral; Humans; Mice; Inbred C57BL; Knockout |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt3wn5714m; https://escholarship.org/uc/item/3wn5714m; https://escholarship.org/content/qt3wn5714m/qt3wn5714m.pdf |
| DOI: |
10.3390/v12080867 |
| Availability: |
https://escholarship.org/uc/item/3wn5714m; https://escholarship.org/content/qt3wn5714m/qt3wn5714m.pdf; https://doi.org/10.3390/v12080867 |
| Rights: |
CC-BY |
| Accession Number: |
edsbas.9B3824A9 |
| Database: |
BASE |