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Journal of General Virology header logo Journal of General Virology

Volume 104, Issue 11

Structure and immunogenicity of the murine astrovirus capsid spike No Access

Abstract

Human astroviruses (HAstVs) are small, non-enveloped icosahedral RNA viruses that are a significant cause of diarrhoea in young children. Despite their worldwide prevalence, HAstV pathogenesis studies and vaccine development remain challenging due to the lack of an animal model for HAstV infection. The recent development of a murine astrovirus (MuAstV) infection model in mice provides the opportunity to test proof-of-concept vaccines based on MuAstV antigens. To help establish a system in which an astrovirus capsid spike-based vaccine could be tested , we designed and produced a recombinant MuAstV capsid spike protein based on predicted secondary structure homology to HAstV spike proteins. The recombinant MuAstV spike can be expressed with high efficiency in and retains antigenicity to polyclonal antibodies elicited by MuAstV infection. We determined the crystal structure of the MuAstV spike to 1.75 Å and assessed its structural conservation with HAstV capsid spike. Despite low sequence identity between the MuAstV and HAstV spikes and differences in their overall shapes, they share related structural folds. Additionally, we found that vaccination with MuAstV spike induced anti-MuAstV-spike antibodies, highlighting that the recombinant spike is immunogenic. These studies lay a foundation for future MuAstV challenge studies to test whether MuAstV spike can be the basis of an effective vaccine.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): astroviruses , murine astrovirus , spike protein , viral capsid and virus structure
Funding
This study was supported by the:
  • National Institute of General Medical Sciences (Award T32 GM133391)
    • Principle Award Recipient: NataliePedicino
  • National Institute of General Medical Sciences (Award T32 GM133391)
    • Principle Award Recipient: SarahLanning
  • Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Award K22 AI156116)
    • Principle Award Recipient: ValerieCortez
  • Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Award R01 AI144090)
    • Principle Award Recipient: RebeccaM. DuBois
© 2023 The Authors
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2023-11-01
2025-05-15
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/content/journal/jgv/10.1099/jgv.0.001913
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Structure and immunogenicity of the murine astrovirus capsid spike
J. Gen. Virol. 104, 001913 (2023); https://doi.org/10.1099/jgv.0.001913
/content/journal/jgv/10.1099/jgv.0.001913
/content/journal/jgv/10.1099/jgv.0.001913
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