Mutations in the H7N9 bird flu virus increase its replication rate and stability in avian cells, but reduce its preference for infecting human cells, a study from The Pirbright Institute has found. The results show that outbreaks in birds caused by strains with these mutations could pose a lower risk to human health, while remaining a significant threat to the poultry industry.
H7N9 low-pathogenicity avian influenza (LPAI) virus usually infects birds, but in 2013 the first human case was recorded in China. Since then, there have been over 1,500 confirmed human infections with about 40 percent of cases resulting in fatalities. Further evolution of the H7N9 virus gave rise to a high-pathogenicity avian influenza (HPAI) strain that could cause 100 percent mortality in chickens. In 2017 the Chinese Government initiated a wide scale vaccination programme in chickens which drove down cases of both low and high pathogenicity strains.
Previous Pirbright research identified three mutations in avian influenza H7N9 viruses that enabled them to overcome immunity generated by vaccines. The mutations altered a protein on the outside of the virus called haemagglutinin (HA), which binds to host cell receptors and allows the virus to enter and cause infection.
In the latest study, published in the Journal of Virology, the team discovered the same mutations occurred in H7N9 viruses isolated from the field in 2019, which most likely emerged in birds that had either been immunised or naturally infected. Analysis of the viruses demonstrated that strains with these mutations have significantly increased replication rates in both chicken cell cultures and chick embryos as well as displaying greater acid and thermal stability, which could improve transmission ability.
The mutations also influenced which animal cells the strain could enter – their HA proteins could still bind to the receptors of bird cells, but they lost their affinity for human cell receptors. These findings show that in evolving to escape the chicken immune system, the mutated H7N9 viruses have reduced their risk to human health whilst increasing the threat they pose to poultry, although further studies in birds are needed to confirm the impact this could have on infection and disease spread.
Professor Munir Iqbal, head of the Avian Influenza Group at Pirbright, said: “Our approach has allowed us to accurately predict avian influenza mutations that appear in the field, and assess how these mutations could affect the risk they pose to both human and avian populations. This information can be used to inform surveillance efforts and provide early warnings of potentially dangerous emerging strains.”
This study was funded by the Biotechnology and Biological Sciences Research Council, part of UK Research and Innovation (BBSRC UKRI), the British Council and the Royal Society as part of the Newton Fund, which was co-funded by National Natural Science Foundation of China (NSFC).
Image: Graphic representation of an influenza virus. The top half is removed to show the genetic material inside. The virus’ surface proteins, haemagglutinin (HA) and neuraminidase (NA), were highlighted in light and dark blue, respectively. Credit: CDC/ Douglas Jordan