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Published on: September 13, 2018
Molecular mechanism underlying B19 virus inactivation and comparison to other parvoviruses
Bernhard Mani1, Marco Gerber, Patricia Lieby
1Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland.
Background:
B19 virus (B19V) is a human pathogen frequently present in blood specimens. Transmission of the virus occurs mainly via the respiratory route, but it has also been shown to occur through the administration of contaminated plasma-derived products. Parvoviridae are highly resistant to physicochemical treatments; however, B19V is more vulnerable than the rest of parvoviruses. The molecular mechanism governing the inactivation of B19V and the reason for its higher vulnerability remain unknown.
Study Design And Methods:
After inactivation of B19V by wet heat and low pH, the integrity of the viral capsid was examined by immunoprecipitation with two monoclonal antibodies directed to the N-terminal of VP1 and to a conformational epitope in VP2. The accessibility of the viral DNA was quantitatively analyzed by a hybridization-extension assay and by nuclease treatment.
Results:
The integrity of the viral particles was maintained during the inactivation procedure; however, the capsids became totally depleted of viral DNA. The DNA-depleted capsids, although not infectious, were able to attach to target cells. Comparison studies with other members of the Parvoviridae family revealed a remarkable instability of B19V DNA in its encapsidated state.
Conclusion:
Inactivation of B19V by heat or low pH is not mediated by capsid disintegration but by the conversion of the infectious virions into DNA-depleted capsids. The high instability of the viral DNA in its encapsidated state is an exclusive feature of B19V, which explains its lower resistance to inactivation treatments.
Insights
The human parvovirus B19 (B19V) is inactivated by heat or low pH through DNA removal from its capsid, not capsid breakdown. This DNA instability explains B19V's vulnerability to inactivation treatments.
Area of Science:
- Virology
- Molecular Biology
- Infectious Diseases
Background:
- Human parvovirus B19 (B19V) is a common pathogen in blood, transmissible via respiratory or contaminated plasma products.
- Parvoviridae are generally resistant to treatments, but B19V shows higher vulnerability, with the underlying mechanism unknown.
Purpose of the Study:
- To elucidate the molecular mechanism of B19V inactivation by heat and low pH.
- To understand the reason for B19V's increased susceptibility to inactivation compared to other parvoviruses.
Main Methods:
- B19V was inactivated using wet heat and low pH treatments.
- Viral capsid integrity was assessed using immunoprecipitation with specific monoclonal antibodies.
- Viral DNA accessibility was quantified via hybridization-extension assays and nuclease treatment.
Main Results:
- Viral particle integrity was preserved post-inactivation, but capsids were completely DNA-depleted.
- DNA-depleted capsids retained the ability to attach to target cells, though they were non-infectious.
- B19V DNA demonstrated significantly greater instability within its encapsidated state compared to other Parvoviridae members.
Conclusions:
- B19V inactivation by heat or low pH occurs via DNA expulsion from intact capsids, not capsid disintegration.
- The unique instability of B19V DNA in its encapsidated form is responsible for its heightened sensitivity to inactivation methods.
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