Virus inactivation and protein modifications by ethyleneimines
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Published on: March 26, 2014
1Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland. kaersemann@ibc.unibe.ch
Abstract:
Virus inactivation by ethyleneimines was first introduced more than 30 years ago. Selective targeting of nucleic acids was reported for oligomeric ethyleneimines. In this study, trimeric ethyleneimine (TEI) was used to inactivate minute virus of mice (MVM; Parvoviridae) and Semliki forest virus (SFV; Togaviridae). The pH-dependency of the inactivation kinetics observed with MVM was different compared to the kinetics reported for other viruses. The higher inactivation rate at higher pH favoured the idea of a mechanism involving protein modifications. Alteration of the isoelectric point and changes in mass could be observed after treatment of soluble proteins with TEI. The uptake of MVM by host cells was reduced or completely blocked by TEI treatment, as shown by monitoring viral internalisation of DNA into target cells. The observed loss of virus infectivity coincided with the inhibition of virus uptake. Thus, virus inactivation by TEI is most likely also a result of chemical modifications of viral surface proteins.
Insights
Trimeric ethyleneimine (TEI) effectively inactivates viruses like minute virus of mice (MVM) and Semliki forest virus (SFV). TEI likely works by chemically modifying viral surface proteins, inhibiting virus uptake into host cells.
Area of Science:
- Virology
- Biochemistry
- Antiviral research
Background:
- Ethyleneimines have been used for virus inactivation for over 30 years.
- Oligomeric ethyleneimines have shown selective targeting of viral nucleic acids.
Purpose of the Study:
- To investigate the efficacy of trimeric ethyleneimine (TEI) in inactivating minute virus of mice (MVM) and Semliki forest virus (SFV).
- To elucidate the mechanism of TEI-mediated virus inactivation, focusing on pH dependency and effects on viral proteins and cell uptake.
Main Methods:
- Treatment of MVM and SFV with TEI.
- Analysis of pH-dependent inactivation kinetics.
- Characterization of TEI-treated soluble viral proteins (isoelectric point, mass).
- Monitoring of viral DNA uptake into host cells after TEI treatment.
Main Results:
- TEI demonstrated inactivation of MVM and SFV.
- MVM inactivation kinetics showed unique pH dependency, suggesting protein modification.
- TEI treatment altered the isoelectric point and mass of soluble viral proteins.
- TEI significantly reduced or blocked MVM uptake into host cells, correlating with infectivity loss.
Conclusions:
- Virus inactivation by TEI is likely mediated by chemical modifications of viral surface proteins.
- Inhibition of virus uptake into host cells is a key factor in TEI-induced virus inactivation.
- TEI presents a potential antiviral strategy targeting viral surface proteins.
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