Human rhinovirus capsid dynamics is controlled by canyon flexibility

Nichole Reisdorph, John J. Thomas, Umesh Katpally, Elaine Chase, Ken Harris, Gary Siuzdak, Thomas J. Smith

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Quantitative enzyme accessibility experiments using nano liquid chromatography electrospray mass spectrometry combined with limited proteolysis and isotope-labeling was used to examine the dynamic nature of the human rhinovirus (HRV) capsid in the presence of three antiviral compounds, a neutralizing Fab, and drug binding cavity mutations. Using these methods, it was found that the antivirals WIN 52084 and picovir (pleconaril) stabilized the capsid, while dansylaziridine caused destabilization. Site-directed mutations in the drug-binding cavity were found to stabilize the HRV14 capsid against proteolytic digestion in a manner similar to WIN 52084 and pleconaril. Antibodies that bind to the NIm-IA antigenic site and penetrate the canyon were also observed to protect the virion against proteolytic cleavage. These results demonstrate that quantifying the effects of antiviral ligands on protein "breathing" can be used to compare their mode of action and efficacy. In this case, it is apparent that hydrophobic antiviral agents, antibodies, or mutations in the canyon region block viral breathing. Therefore, these studies demonstrate that mobility in the canyon region is a major determinant in capsid breathing.

Original languageEnglish (US)
Pages (from-to)34-44
Number of pages11
JournalVirology
Volume314
Issue number1
DOIs
StatePublished - Sep 15 2003
Externally publishedYes

Keywords

  • Mass spectrometry
  • Rhinovirus
  • Virus maturation

ASJC Scopus subject areas

  • Virology

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  • Cite this

    Reisdorph, N., Thomas, J. J., Katpally, U., Chase, E., Harris, K., Siuzdak, G., & Smith, T. J. (2003). Human rhinovirus capsid dynamics is controlled by canyon flexibility. Virology, 314(1), 34-44. https://doi.org/10.1016/S0042-6822(03)00452-5