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Cellular calpain proteases can cleave the enteroviral polyprotein

Research highlights the potential of calpain inhibitor as an antiviral against enteroviruses

University of Jyväskylä - Jyväskylän yliopisto

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IMAGE: M.Sc Mira Laajala view more 

Credit: The University of Jyvaskyla, Finland

Despite their prevalence, there are no antivirals on the market against enteroviruses, and vaccines have been developed only against couple of serotypes. The production of vaccines against all enterovirus serotypes is not feasible, and so antiviral drugs may be the solution for most of the enterovirus infections.

''For antiviral development, it is crucial to obtain detailed information about factors that contribute to efficient infection. In the future, these factors could then be the targets of antiviral development'', says Mira Laajala.

The information of Mira Laajala's research can potentially be used in the antiviral development against enterovirus infections. The research showed that in addition to viral proteases, cellular calpain proteases can cleave the enteroviral polyprotein.

''This was shown in an in vitro study, but it gives a good starting point to study the phenomenon also in the cells during infection. In addition, a synthetic inhibitor against calpains was shown to prevent enterovirus infection in cells, which highlights the potential of calpain inhibitor as an antiviral against enteroviruses'', says Laajala.

New infectious intermediate particle was found in the research

Mira Laajala found also another cellular factor that contributed to enteroviruses infection. The study showed that cellular vimentin protein formed a cage-like structure around the replicating viral RNA and viral non-structural proteins during infection. In addition, it was revealed that the formation of vimentin cage was needed for efficient production of these viral non-structural proteins.

''This is an interesting finding since the non-structural proteins are the ones that are contributing to the pathogenesis of the virus'', says Mira Laajala.

In addition to the cellular factors, Laajala studied also the uncoating of the virus, so the step where viral RNA is released out from the capsid. The study revealed a new more open, but still infectious particle form. ''Uncoating intermediate particles have been described for enteroviruses before, but our new particle differed from those particles as it still contained all the capsid proteins and was able to bind on the receptor protein on the cell surface and cause infection'', says Laajala.

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The dissertation is published JYU Dissertations series, number 146, ISSN 2489-9003; 146, ISBN 978-951-39-7896-9 (PDF). Link to publication http://urn.fi/URN:ISBN:978-951-39-7896-9

FM Mira Laajala defends her doctoral dissertation in Cell and Molecular Biology "Cellular and viral factors promoting efficient enterovirus uncoating and replication" on Friday 22nd of November at 12:00 at lecture hall YAA303 The Department of Biological and Environmental Sciences (Ylistönrinne, Survontie 9). Opponent is Dr. Marco Vignuzzi from Pasteur Institute, France and Custos is Docent Varpu Marjomäki from the University of Jyväskylä. The doctoral dissertation is held in English.

For further information:

M.Sc Mira Laajala, mira.a.laajala@jyu.fi
Communication officer Tanja Heikkinen, tanja.s.heikkinen@jyu.fi, tel. +358 50 581 8351
https://www.jyu.fi/science/en
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