A transgenic mouse has been developed by researchers in Germany with the aim of identifying new influenza virus strains that have the possibility to cause a global pandemic.
When influenza A viruses are transmitted from birds, pigs, or other animal species to humans, they can cause devastating pandemics. Influenza strains must attain mutations to be able to cross the species barrier and launch themselves at the human population. These mutations enable them to possible evade the innate immune protein MxA and definitely other components of the human immune system. The MxA protein protects cultured human cells from avian influenza viruses but is unfortunately not effective against strains that have developed the capacity to infect humans.
Peter Staeheli and his colleagues at the Institute of Virology, Medical Center University of Freiburg set out to determine if MxA provides a comparable barrier to cross-species infection in vivo.
To achieve this, they opted not to create mouse MxA, but created transgenic mice that express human MxA. They found that the transgenic mice were susceptible to flu viruses of human origin, but resistant to avian influenza viruses. These results were similar to those achieved with cultured human cells.
The virus’ ability to infect human cells has been linked to mutations in the nucleoprotein that encapsulates the virus’ genome. It is thought that MxA targets influenza A by binding to this nucleoprotein. Staeheli’s team engineered an avian influenza virus to contain these mutations and determined that it was able to cause disease in and infect the transgenic mice expressing human MxA.
Although MxA is a barrier against cross species influenza A infection, the virus can evade this barrier easily by creating a few mutations in its nucleoprotein. Staeheli is of the opinion that the transgenic mice can be used to monitor the possible dangers of emerging viral strains. He noted that the MxA transgenic mouse could easily distinguish between virus strains that can evade MxA restriction and MxA sensitive influenza virus strains. The strains that can evade MxA restriction have a high pandemic potential for humans.
Current risk assessment strategies of emerging influenza viruses could be complemented by such analyses, including screening for alterations in known viral virulence genes and viral genome sequencing.
The full study was published in the Journal of Experimental Medicine.