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 editors: Domanska, Aušra; Plavec, Zlatka; Ruokolainen, Visa; Löflund, Benita; Marjomäki, Varpu; Butcher, Sarah J.
Journal or series: Journal of Virology
ISSN: 0022-538X
eISSN: 1098-5514
Publication year: 2022
Publication date: 30/11/2022
Volume: 96
Issue number: 24
Pages range: e01367-22
Publisher: American Society for Microbiology
Publication country: United States
Publication language: English
DOI: https://doi.org/10.1128/jvi.01367-22
Publication open access: Openly available
Publication channel open access: Partially 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.
Free keywords: A-particle; albumin; cryo-EM; endosomal ionic composition; virus structure
Contributing organizations
Ministry reporting: Yes
Reporting Year: 2022
JUFO rating: 2