Research led by The Pirbright Institute has shown mutant H9N2 bird flu viruses isolated from Pakistan are able to escape immune responses and adapt to infect humans. This could result in reduced vaccine efficiency and the possibility of human outbreaks.
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.
This research was funded by the BBSRC under Zoonoses and Emerging Livestock Systems (ZELS) programme.
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About The Pirbright Institute
The Pirbright Institute is a world leading centre of excellence in research and surveillance of virus diseases of farm animals and viruses that spread from animals to humans. Based in the UK and receiving strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC), the Institute works to enhance capability to contain, control and eliminate these economically and medically important diseases through highly innovative fundamental and applied bioscience.
With an annual income of nearly £32.1 million from grants and commercial activity, and a total of £14.3 million strategic investment from BBSRC during 2017-2018, the Institute contributes to global food security and health, improving quality of life for animals and people.
For more information about The Pirbright Institute see: www.pirbright.ac.uk
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