While the avian influenza viruses H5N1 and H5N7 are the most reported for human infections, H9N2, which is widely spread in the Middle East and Southeast Asia, has also been found in humans, although symptoms are usually mild, and infection is not known to have resulted in any deaths.

Mutant avian influenza H9N2 viruses isolated in Pakistan, however, have been found capable of escaping immune responses and adapting to infect humans. This ability could result in reduced vaccine efficiency and the possibility of human outbreaks.

Scientists led by the U.K.’s Pirbright Institute carrying out surveillance and research have found small changes to the haemagglutinin of the H9N2 virus enabling the virus to enter human cells.

The study found that the mutant virus can bind to human-type cell receptors, although its preference is still for avian-like receptors.

The H9N2 virus causes only moderate illness and death rates in domestic poultry, and does not cause severe disease in humans, however, the capacity of an H9N2 avian influenza virus to bind to human-like receptors raises concerns for potential human transmission.

The team also found that the mutation prevents antibodies from binding to and neutralizing the virus. It enhances H9N2 haemagglutinin affinity for host cell receptors, which out-competes antibody binding, preventing the virus from being neutralized and this could lead to lowered protection for chickens that have been vaccinated against H9N2 viruses.

Learning opportunity?

Influenza viruses have a relatively high mutation rate, but it is worth remembering that the H5N1 virus, which has undergone numerous mutations, emerged in poultry as highly pathogenic in China in 1996 and in Hong Kong in humans the following year. Leaving damage to the poultry industry aside, since 2003, it has resulted in 860 human infections and 454 deaths, while between 2013 and early 2017, H7N9 was responsible for 1,223 human infections.

While concerning, this mutation of the H9N2 virus has brought limitations with it. The mutant virus was found to be unable to replicate in cell cultures efficiently, showing the balance influenza viruses must maintain when mutations occur that enable them to escape the immune system and infect different hosts.

The researchers note that many mutations result in a virus unable to effectively replicate. However, occasionally these changes leave the virus unhindered, allowing it to spread rapidly.

The research group is now looking at how this mutant virus could further mutate to hit the right balance while retaining its ability to bind to human-like receptors. This information would facilitate better screening of circulating avian influenza viruses for traits that may allow them to infect humans, so providing early warning of their pandemic potential.