Salt Enhances the Thermostability of Enteroviruses by Stabilizing Capsid Protein Interfaces
| Autor: | Matteo Dal Peraro, Simon Meister, Alessio Prunotto, Tamar Kohn |
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| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Pentamer viruses Immunology Protomer Sodium Chloride 010501 environmental sciences Coxsackievirus medicine.disease_cause 01 natural sciences Microbiology Cell Line 03 medical and health sciences symbols.namesake Virology Chlorocebus aethiops medicine Animals Enterovirus 030304 developmental biology 0105 earth and related environmental sciences Thermostability 0303 health sciences biology Protein Stability Structure and Assembly Poliovirus Temperature Hydrogen-Ion Concentration biology.organism_classification Capsid 13. Climate action Insect Science symbols Biophysics Capsid Proteins van der Waals force |
| Zdroj: | J Virol |
| ISSN: | 1098-5514 0022-538X |
| Popis: | Enteroviruses are common agents of infectious disease that are spread by the fecal-oral route. They are readily inactivated by mild heat, which causes the viral capsid to disintegrate or undergo conformational change. While beneficial for the thermal treatment of food or water, this heat sensitivity poses challenges for the stability of enterovirus vaccines. The thermostability of an enterovirus can be modulated by the composition of the suspending matrix, though the effects of the matrix on virus stability are not understood. Here, we determined the thermostability of four enterovirus strains in solutions with various concentrations of NaCl and different pH values. The experimental findings were combined with molecular modeling of the protein interaction forces at the pentamer and the protomer interfaces of the viral capsids. While pH only had a modest effect on thermostability, increasing NaCl concentrations raised the breakpoint temperatures of all viruses tested by up to 20°C. This breakpoint shift could be explained by an enhancement of the van der Waals attraction forces at the two protein interfaces. In comparison, the (net repulsive) electrostatic interactions were less affected by NaCl. Depending on the interface considered, the breakpoint temperature shifted by 7.5 or 5.6°C per 100-kcal/(mol·A) increase in protein interaction force. IMPORTANCE The genus Enterovirus encompasses important contaminants of water and food (e.g., coxsackieviruses), as well as viruses of acute public health concern (e.g., poliovirus). Depending on the properties of the surrounding matrix, enteroviruses exhibit different sensitivities to heat, which in turn influences their persistence in the environment, during food treatment, and during vaccine storage. Here, we determined the effect of NaCl and pH on the heat stability of different enteroviruses and related the observed effects to changes in protein interaction forces in the viral capsid. We demonstrate that NaCl renders enteroviruses thermotolerant and that this effect stems from an increase in van der Waals forces at different protein subunits in the viral capsid. This work sheds light on the mechanism by which salt enhances virus stability. |
| Databáze: | OpenAIRE |
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