Published in the journal Emerging Infectious Diseases, Pirbright scientists carrying out surveillance research discovered that small changes to a surface protein, called haemagglutinin, of the H9N2 influenza A virus, enables the mutated virus to enter human cells.

Influenza viruses that infect humans and chickens typically use different host cell receptors in the early attachment stage. Professor Munir Iqbal, head of the Avian Influenza group at Pirbright said: “In this study, we demonstrated the mutant can bind to human-type cell receptors, but its preference for avian-like receptors remains. H9N2 viruses cause moderate illness and death rates in domestic poultry and do not cause severe disease in humans, but the capability of an H9N2 avian influenza virus to bind to human-like receptors raises concern for potential human transmission.”

Haemagglutinin is used by influenza viruses to enter host cells to begin replication, which makes it a prime target for the immune system. The team also found that the mutation, which is a single amino acid substitution, prevents antibodies from binding and neutralising the virus. The mutation enhances the H9N2 haemagglutinin affinity for host cell receptors, which out-competes antibody binding, preventing the virus from being neutralised. This could result in lowered protection for chickens that have been vaccinated against H9N2 viruses.

However, mutations such as these come at a cost for the virus. The mutant H9N2 virus did not replicate in cell cultures as efficiently as viruses without the amino acid substitution. This shows the fine balance influenza viruses must maintain when mutations occur that enable them to escape the immune system and infect different hosts; many mutations will result in a virus which is unable to effectively replicate. However, occasionally these changes leave the virus unhindered, allowing it to spread rapidly.

The group is now working on understanding how this mutant H9N2 avian influenza A virus could generate a mutation that hits the right balance whilst retaining its ability to bind to human-like receptors. Having this information will allow better screening of circulating avian influenza viruses for traits that may allow them to infect humans, providing early warning as to their pandemic potential.

As reported by the Pirbright Institute