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New mouse developed that could provide advance warning of next flu pandemic

Date:
April 10, 2017
Source:
The Rockefeller University Press
Summary:
A transgenic mouse has been developed that could help scientists identify new influenza virus strains with the potential to cause a global pandemic.
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Cells from a transgenic mouse expressing human MxA (red).
Credit: Deeg et al., 2017

Researchers in Germany have developed a transgenic mouse that could help scientists identify new influenza virus strains with the potential to cause a global pandemic. The mouse is described in a study, "In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein," that will be published April 10 in The Journal of Experimental Medicine.

Influenza A viruses can cause devastating pandemics when they are transmitted to humans from pigs, birds, or other animal species. To cross the species barrier and establish themselves in the human population, influenza strains must acquire mutations that allow them to evade components of the human immune system, including, perhaps, the innate immune protein MxA. This protein can protect cultured human cells from avian influenza viruses but is ineffective against strains that have acquired the ability to infect humans.

To investigate whether MxA provides a similar barrier to cross-species infection in vivo, Peter Staeheli and colleagues at the Institute of Virology, Medical Center University of Freiburg, created transgenic mice that express human, rather than mouse, MxA. Similar to the results obtained with cultured human cells, the transgenic mice were resistant to avian influenza viruses but susceptible to flu viruses of human origin.

MxA is thought to target influenza A by binding to the nucleoprotein that encapsulates the virus' genome, and mutations in this nucleoprotein have been linked to the virus' ability to infect human cells. Staeheli and colleagues found that an avian influenza virus engineered to contain these mutations was able to infect and cause disease in the transgenic mice expressing human MxA.

MxA is therefore a barrier against cross-species influenza A infection, but one that the virus can evade through a few mutations in its nucleoprotein. Staeheli and colleagues think that their transgenic mice could help monitor the potential dangers of emerging viral strains. "Our MxA-transgenic mouse can readily distinguish between MxA-sensitive influenza virus strains and virus strains that can evade MxA restriction and, consequently, possess a high pandemic potential in humans," Staeheli says. "Such analyses could complement current risk assessment strategies of emerging influenza viruses, including viral genome sequencing and screening for alterations in known viral virulence genes."


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Materials provided by The Rockefeller University Press. Note: Content may be edited for style and length.


Journal Reference:

  1. Christoph M. Deeg, Ebrahim Hassan, Pascal Mutz, Lara Rheinemann, Veronika Götz, Linda Magar, Mirjam Schilling, Carsten Kallfass, Cindy Nürnberger, Sébastien Soubies, Georg Kochs, Otto Haller, Martin Schwemmle, Peter Staeheli. In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein. The Journal of Experimental Medicine, 2017; jem.20161033 DOI: 10.1084/jem.20161033

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The Rockefeller University Press. "New mouse developed that could provide advance warning of next flu pandemic." ScienceDaily. ScienceDaily, 10 April 2017. <www.sciencedaily.com/releases/2017/04/170410095845.htm>.
The Rockefeller University Press. (2017, April 10). New mouse developed that could provide advance warning of next flu pandemic. ScienceDaily. Retrieved May 26, 2017 from www.sciencedaily.com/releases/2017/04/170410095845.htm
The Rockefeller University Press. "New mouse developed that could provide advance warning of next flu pandemic." ScienceDaily. www.sciencedaily.com/releases/2017/04/170410095845.htm (accessed May 26, 2017).

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