Novel mouse model developed to identify zoonotic potential of influenza A strains

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Researchers from the University of Freiburg (Germany) have developed a novel mouse model that could assist in the discovery of new influenza virus strains. The results from this study, recently published in The Journal of Experimental Medicine, could help scientists identify strains that have the potential to cause a global pandemic.

Predicting the pandemic potential of zoonotic influenza A viruses is currently an impossible task – for cross species transmission to occur, influenza strains must acquire mutations that enable them to overcome the human immune response.

MxA is an innate immune protein demonstrated to protect cultured human cells from avian influenza viruses, but it does not have the ability to create the same barrier to strains that infect humans. It is thought that MxA targets influenza A by binding to the nucleoprotein encapsulating the virus’ genome and that the virus’ ability to transmit to human cells is linked to mutations occurring in this nucleoprotein.

In this study Peter Staeheli and colleagues (University of Freiburg) set to determine if MxA could produce a similar barrier to cross-species infection in vivo. The team developed transgenic mice expressing human MxA and discovered they carried resistance to avian influenza viruses but not to human influenza viruses.

The team also discovered that avian influenza viruses, engineered to contain mutations in the nucleoprotein, could infect the transgenic mice expressing human MxA. It was therefore concluded that MxA acts as a barrier to cross-species influenza A infection, a barrier that the virus can overcome by acquiring mutations in its nucleoprotein.

Staeheli commented: “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. 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.”

Sources:  Deeg CM, Hassan E, Mutz P, et al. In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein. J. Exp. Med. doi:10.1084/jem.20161033 (2017); www.eurekalert.org/pub_releases/2017-04/rup-rdm040417.php

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