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Updated: Jul 24, 2025

Generation and Assembly of Virus-Specific Nucleocapsids of the Respiratory Syncytial Virus
Published on: July 27, 2021
Enterovirus D68 capsid formation and stability requires acidic compartments
Ganna Galitska1, Alagie Jassey1, Michael A Wagner1
1Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 W. Baltimore St, Baltimore, MD 21201, USA.
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 (AFM). 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 3-4hpi, 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.
Insights
Enterovirus D68 requires specific organelle acidification for capsid formation. Inhibiting this process disrupts viral replication and causes cellular changes, unlike poliovirus.
Area of Science:
- Virology
- Cell Biology
Background:
- Enterovirus D68 (EV-D68) is a picornavirus linked to acute flaccid myelitis (AFM).
- Understanding EV-D68 pathogenesis is limited, often relying on poliovirus models.
- Low pH promotes poliovirus capsid maturation, but EV-D68's requirements are less understood.
Approach:
- Investigated the role of compartment acidification in EV-D68 infection.
- Examined cellular and viral phenotypes upon inhibition of acidification.
- Identified a critical time window for acidification's role in EV-D68 lifecycle.
Key Points:
- Inhibiting compartment acidification during a specific window (3-4hpi) impairs EV-D68 capsid formation and maintenance.
- This leads to altered viral replication organelles clustering.
- Acidification is crucial during the transition from RNA replication to virion assembly.
Conclusions:
- EV-D68 has distinct acidification requirements compared to poliovirus.
- Compartment acidification is a critical, time-sensitive step in EV-D68 virion production.
- Findings reveal novel insights into EV-D68 replication dynamics and potential therapeutic targets.
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