An international team of scientists has identified several genetic mutations that could, should they arise, potentially allow the avian influenza strain H7N9 to cross the species barrier and spread between humans.
H7N9 is a strain of flu virus that normally infects birds, but has spread to at least 779 humans in a number of outbreaks related to poultry markets.
The virus is not capable of spreading sustainably from human to human, but scientists are concerned it could potentially mutate into a form that can.
To investigate this possibility, James Paulson and colleagues from the Scripps Research Institute in California, US analysed mutations that could occur in H7N9’s genome.
In flu strains that circulate in avian viruses, different subtypes exist of a protein called haemagglutinin, ranging from H1 to H16. So far, three subtypes have been found in human flu viruses – H1, H2 and H3.
In this research, efforts were focused on a gene that codes for H7, which is found on the surface of flu viruses and allows them to latch on to host cells.
As with other avian flu viruses, H7N9 is specific for receptors on bird cells, but not receptors on human cells. However, a transition to human specificity could enable H7N9 to circulate among humans, just like other human flu strains that have caused pandemics in the past.
Using molecular modelling and knowledge of haemagglutinin’s structure, the team identified mutations that would change the protein’s amino acid sequence, causing a switch to human specificity.
They then produced the haemagglutinin with different combinations of these mutations in an experimental cell line, as testing the mutations in H7N9 viruses themselves can be dangerous.
From these cells, scientists harvested the mutant haemagglutinin proteins, and tested how strongly they bound to human-type and bird-type receptors.
It was found several forms with mutations in three amino acids bound far more strongly to human receptors, which meant they had switched specificity from bird to human. The triple-mutant H7 haemagglutinins also successfully latched on to cells in samples of human trachea tissue.
Safety regulations prohibit introducing these mutations to actual H7N9 viruses, limiting scientists’ ability to test their effects in animals.
Nonetheless, the research team suggests keeping an eye out for the development of these mutations in humans infected with H7N9 could help trigger a timely response to prevent potential spread.
- Their findings are published in PLOS Pathogens.