A1 Journal article (refereed)
Structural Studies Reveal that Endosomal Cations Promote Formation of Infectious Coxsackievirus A9 A-Particles, Facilitating RNA and VP4 Release (2022)


Domanska, A., Plavec, Z., Ruokolainen, V., Löflund, B., Marjomäki, V., & Butcher, S. J. (2022). Structural Studies Reveal that Endosomal Cations Promote Formation of Infectious Coxsackievirus A9 A-Particles, Facilitating RNA and VP4 Release. Journal of Virology, 96(24), e01367-22. https://doi.org/10.1128/jvi.01367-22


JYU authors or editors


Publication details

All authors or editorsDomanska, Aušra; Plavec, Zlatka; Ruokolainen, Visa; Löflund, Benita; Marjomäki, Varpu; Butcher, Sarah J.

Journal or seriesJournal of Virology

ISSN0022-538X

eISSN1098-5514

Publication year2022

Publication date30/11/2022

Volume96

Issue number24

Pages rangee01367-22

PublisherAmerican Society for Microbiology

Publication countryUnited States

Publication languageEnglish

DOIhttps://doi.org/10.1128/jvi.01367-22

Publication open accessOpenly available

Publication channel open accessPartially open access channel

Publication is parallel published (JYX)https://jyx.jyu.fi/handle/123456789/84401


Abstract

Coxsackievirus A9 (CVA9), an enterovirus, is a common cause of pediatric aseptic meningitis and neonatal sepsis. During cell entry, enterovirus capsids undergo conformational changes leading to expansion, formation of large pores, externalization of VP1 N termini, and loss of the lipid factor from VP1. Factors such as receptor binding, heat, and acidic pH can trigger capsid expansion in some enteroviruses. Here, we show that fatty acid-free bovine serum albumin or neutral endosomal ionic conditions can independently prime CVA9 for expansion and genome release. Our results showed that CVA9 treatment with albumin or endosomal ions generated a heterogeneous population of virions, which could be physically separated by asymmetric flow field flow fractionation and computationally by cryo-electron microscopy (cryo-EM) and image processing. We report cryo-EM structures of CVA9 A-particles obtained by albumin or endosomal ion treatment and a control nonexpanded virion to 3.5, 3.3, and 2.9 Å resolution, respectively. Whereas albumin promoted stable expanded virions, the endosomal ionic concentrations induced unstable CVA9 virions which easily disintegrated, losing their genome. Loss of most of the VP4 molecules and exposure of negatively charged amino acid residues in the capsid’s interior after expansion created a repulsive viral RNA-capsid interface, aiding genome release.


Keywordsvirusesalbumens

Free keywordsA-particle; albumin; cryo-EM; endosomal ionic composition; virus structure


Contributing organizations


Ministry reportingYes

Reporting Year2022

JUFO rating2


Last updated on 2024-25-03 at 09:13