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Published on: October 3, 2016
Studies on the inactivation of human parvovirus 4
Sally A Baylis1, Philip W Tuke, Eiji Miyagawa
1Paul-Ehrlich-Institut, Langen, Germany.
Background:
Human parvovirus 4 (PARV4) is a novel parvovirus, which like parvovirus B19 (B19V) can be a contaminant of plasma pools used to prepare plasma-derived medicinal products. Inactivation studies of B19V have shown that it is more sensitive to virus inactivation strategies than animal parvoviruses. However, inactivation of PARV4 has not yet been specifically addressed.
Study Design And Methods:
Treatment of parvoviruses by heat or low-pH conditions causes externalization of the virus genome. Using nuclease treatment combined with real-time polymerase chain reaction, the extent of virus DNA externalization was used as an indirect measure of the inactivation of PARV4, B19V, and minute virus of mice (MVM) by pasteurization of albumin and by low-pH treatment. Infectivity studies were performed in parallel for B19V and MVM.
Results:
PARV4 showed greater resistance to pasteurization and low-pH treatment than B19V, although PARV4 was not as resistant as MVM. There was a 2- to 3-log reduction of encapsidated PARV4 DNA after pasteurization and low-pH treatment. In contrast, B19V was effectively inactivated while MVM was stable under these conditions. Divalent cations were found to have a stabilizing effect on PARV4 capsids. In the absence of divalent cations, even at neutral pH, there was a reduction of PARV4 titer, an effect not observed for B19V or MVM.
Conclusion:
In the case of heat treatment and incubation at low pH, PARV4 shows intermediate resistance when compared to B19V and MVM. Divalent cations seem important for stabilizing PARV4 virus particles.
Insights
Human parvovirus 4 (PARV4) is more resistant to heat and low pH than parvovirus B19 (B19V). Divalent cations stabilize PARV4, impacting its inactivation during plasma product manufacturing.
Area of Science:
- Virology
- Molecular Biology
- Biochemistry
Background:
- Human parvovirus 4 (PARV4) is a novel parvovirus.
- PARV4 can contaminate plasma pools for medicinal products.
- PARV4 inactivation is not well-studied, unlike parvovirus B19 (B19V).
Purpose of the Study:
- To investigate the inactivation of PARV4 under conditions relevant to plasma processing.
- To compare the resistance of PARV4 to B19V and minute virus of mice (MVM).
Main Methods:
- Assessed PARV4, B19V, and MVM inactivation using pasteurization and low-pH treatments.
- Measured viral DNA externalization via nuclease treatment and real-time PCR as an indirect inactivation measure.
- Performed parallel infectivity studies for B19V and MVM.
Main Results:
- PARV4 demonstrated intermediate resistance to pasteurization and low pH, being more resistant than B19V but less than MVM.
- Pasteurization and low-pH treatment reduced encapsidated PARV4 DNA by 2-3 logs.
- Divalent cations stabilized PARV4 capsids, reducing inactivation at neutral pH.
Conclusions:
- PARV4 exhibits intermediate resistance to heat and low-pH inactivation compared to B19V and MVM.
- Divalent cations play a crucial role in stabilizing PARV4 virus particles.
