Enterovirus D68 capsid formation and stability requires acidic compartments
ABSTRACT Enterovirus D68 (EV-D68), a picornavirus traditionally associated with respiratory infections, has recently been linked to a polio-like paralytic condition known as acute flaccid myelitis. EV-D68 is understudied, and much of the field’s understanding of this virus is based on studies of pol...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-10-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.02141-23 |
| _version_ | 1797619697057792000 |
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| author | Ganna Galitska Alagie Jassey Michael A. Wagner Noah Pollack Katelyn Miller William T. Jackson |
| author_facet | Ganna Galitska Alagie Jassey Michael A. Wagner Noah Pollack Katelyn Miller William T. Jackson |
| author_sort | Ganna Galitska |
| collection | DOAJ |
| description | ABSTRACT Enterovirus D68 (EV-D68), a picornavirus traditionally associated with respiratory infections, has recently been linked to a polio-like paralytic condition known as acute flaccid myelitis. EV-D68 is understudied, and much of the field’s understanding of this virus is based on studies of poliovirus. For poliovirus, we previously showed that low pH promotes virus capsid maturation, but here we show that, for EV-D68, inhibition of compartment acidification during a specific window of infection causes a defect in capsid formation and maintenance. These phenotypes are accompanied by radical changes in the infected cell, with viral replication organelles clustering in a tight juxtanuclear grouping. Organelle acidification is critical during a narrow window from 3 to 4 hpi, which we have termed the “transition point,” separating translation and peak RNA replication from capsid formation, maturation, and egress. Our findings highlight that acidification is crucial only when vesicles convert from RNA factories to virion crucibles. IMPORTANCE The respiratory picornavirus enterovirus D68 is a causative agent of acute flaccid myelitis, a childhood paralysis disease identified in the last decade. Poliovirus, another picornavirus associated with paralytic disease, is a fecal-oral virus that survives acidic environments when passing from host to host. Here, we follow up on our previous work showing a requirement for acidic intracellular compartments for maturation cleavage of poliovirus particles. Enterovirus D68 requires acidic vesicles for an earlier step, assembly, and maintenance of viral particles themselves. These data have strong implications for the use of acidification blocking treatments to combat enterovirus diseases. |
| first_indexed | 2024-03-11T08:30:30Z |
| format | Article |
| id | doaj.art-82ad6c3c19fc47e3af060dd91faf355b |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-03-11T08:30:30Z |
| publishDate | 2023-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-82ad6c3c19fc47e3af060dd91faf355b2023-11-16T21:48:01ZengAmerican Society for MicrobiologymBio2150-75112023-10-0114510.1128/mbio.02141-23Enterovirus D68 capsid formation and stability requires acidic compartmentsGanna Galitska0Alagie Jassey1Michael A. Wagner2Noah Pollack3Katelyn Miller4William T. Jackson5Department of Microbiology and Immunology, University of Maryland School of Medicine , Baltimore, Maryland, USADepartment of Microbiology and Immunology, University of Maryland School of Medicine , Baltimore, Maryland, USADepartment of Microbiology and Immunology, University of Maryland School of Medicine , Baltimore, Maryland, USADepartment of Microbiology and Immunology, University of Maryland School of Medicine , Baltimore, Maryland, USADepartment of Microbiology and Immunology, University of Maryland School of Medicine , Baltimore, Maryland, USADepartment of Microbiology and Immunology, University of Maryland School of Medicine , Baltimore, Maryland, USAABSTRACT Enterovirus D68 (EV-D68), a picornavirus traditionally associated with respiratory infections, has recently been linked to a polio-like paralytic condition known as acute flaccid myelitis. EV-D68 is understudied, and much of the field’s understanding of this virus is based on studies of poliovirus. For poliovirus, we previously showed that low pH promotes virus capsid maturation, but here we show that, for EV-D68, inhibition of compartment acidification during a specific window of infection causes a defect in capsid formation and maintenance. These phenotypes are accompanied by radical changes in the infected cell, with viral replication organelles clustering in a tight juxtanuclear grouping. Organelle acidification is critical during a narrow window from 3 to 4 hpi, which we have termed the “transition point,” separating translation and peak RNA replication from capsid formation, maturation, and egress. Our findings highlight that acidification is crucial only when vesicles convert from RNA factories to virion crucibles. IMPORTANCE The respiratory picornavirus enterovirus D68 is a causative agent of acute flaccid myelitis, a childhood paralysis disease identified in the last decade. Poliovirus, another picornavirus associated with paralytic disease, is a fecal-oral virus that survives acidic environments when passing from host to host. Here, we follow up on our previous work showing a requirement for acidic intracellular compartments for maturation cleavage of poliovirus particles. Enterovirus D68 requires acidic vesicles for an earlier step, assembly, and maintenance of viral particles themselves. These data have strong implications for the use of acidification blocking treatments to combat enterovirus diseases.https://journals.asm.org/doi/10.1128/mbio.02141-23picornavirusesautophagyenterovirus D68polioviruscellular acidificationvirion assembly |
| spellingShingle | Ganna Galitska Alagie Jassey Michael A. Wagner Noah Pollack Katelyn Miller William T. Jackson Enterovirus D68 capsid formation and stability requires acidic compartments mBio picornaviruses autophagy enterovirus D68 poliovirus cellular acidification virion assembly |
| title | Enterovirus D68 capsid formation and stability requires acidic compartments |
| title_full | Enterovirus D68 capsid formation and stability requires acidic compartments |
| title_fullStr | Enterovirus D68 capsid formation and stability requires acidic compartments |
| title_full_unstemmed | Enterovirus D68 capsid formation and stability requires acidic compartments |
| title_short | Enterovirus D68 capsid formation and stability requires acidic compartments |
| title_sort | enterovirus d68 capsid formation and stability requires acidic compartments |
| topic | picornaviruses autophagy enterovirus D68 poliovirus cellular acidification virion assembly |
| url | https://journals.asm.org/doi/10.1128/mbio.02141-23 |
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