Comparative molecular biology approaches for the production of poliovirus virus-like particles using Pichia pastoris.

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dc.contributor.authorSherry, Lee
dc.contributor.authorGrehan, Keith
dc.contributor.authorSnowden, Joseph
dc.contributor.authorKnight, Michael
dc.contributor.authorAdeyemi, Oluwapelumi
dc.contributor.authorRowlands, David
dc.contributor.authorStonehouse, Nicola
dc.date.accessioned2021-08-24T11:03:24Z
dc.date.available2021-08-24T11:03:24Z
dc.date.issued2020
dc.description.abstractFor enteroviruses such as poliovirus (PV), empty capsids, which are antigenically indistinguishable from mature virions, are produced naturally during viral infection. The production of such capsids recombinantly, in heterologous systems such as yeast, have great potential as virus-like particle (VLP) vaccine candidates. Here, using PV as an exemplar, we show the production of VLPs in Pichia pastoris by coexpression of the structural precursor protein P1 and the viral protease 3CD. The level of expression of the potentially cytotoxic protease relative to that of the P1 precursor was modulated by three different approaches: expression of the P1 precursor and protease from different transcription units, separation of the P1 and protease proteins using the Thosea asigna virus (TaV) 2A translation interruption sequence, or separation of the P1 and protease-coding sequences by an internal ribosome entry site sequence from Rhopalosiphum padi virus (RhPV). We also investigate the antigenicity of VLPs containing previously characterized mutations when produced in Pichia. Finally, using transmission electron microscopy and twodimensional classification, we show that Pichia-derived VLPs exhibited the classical icosahedral capsid structure displayed by enteroviruses.en_US
dc.description.sponsorshipThis work was funded via WHO 2019/883397-O, “Generation of virus free polio vaccine–phase IV.” J.S.S. is funded by a Wellcome Trust Ph.D. studentship (102174/B/13/Z).en_US
dc.identifier.citation5. Sherry L., Grehan K., Snowden J.S., Knight M.L., Adeyemi O.O., Rowlands D.J. and Stonehouse N.J. (2020). Comparative molecular biology approaches for the production of poliovirus virus-like particles using Pichia pastoris. mSphere. 5(2); e00838-19en_US
dc.identifier.urihttps://uilspace.unilorin.edu.ng/handle/20.500.12484/6262
dc.language.isoenen_US
dc.publisherMicrobiology Society, UK.en_US
dc.titleComparative molecular biology approaches for the production of poliovirus virus-like particles using Pichia pastoris.en_US
dc.typeArticleen_US

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