Mutant H9N2 Avian Influenza viruses isolated from Pakistan are able to escape immune responses and adapt to infect humans.
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 Avian 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. Haemagglutinin surface protein 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, could result in lowered protection for chickens that have been vaccinated against H9N2 viruses. The mutation enhances the H9N2 haemagglutinin affinity for host cell receptors, which out-competes antibody binding, preventing the virus from being neutralised.
However, mutations such as these come at a cost for the virus. The team found that the mutant H9N2 Avian Influenza 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 virus could generate a mutation that hits the right balance whilst retaining its ability to bind to human-like receptors.