H7N9 bird flu virus prefers to infect birds to humans

20 June 2013

Crystal structure of H7N9 haemagglutinin

Image: Crystal structure of H7N9 haemagglutinin showing the human receptor model in the receptor binding site.

New research from the MRC's National Institute of Medical Research (now part of the Francis Crick Institute)  reveals that the current H7N9 bird flu virus circulating in China has not acquired a preference for human hosts over birds. 

Since the first case of H7N9 infection in humans was reported in February 2013, there have been 132 confirmed cases and 37 deaths, all in, or acquired in, mainland China. There is no evidence of sustained transmission between people and all of the infections seem to have come from infected poultry.

Flu viruses are categorised into types A, B and C. Type A viruses are categorised depending on two proteins on their surface - called haemagglutinin (H) and neuraminidase (N). There are many different combinations of H and N, such as H7N9 avian influenza - commonly known as a type of bird flu.  

The haemagglutinin is responsible for the virus binding to host cells through its interactions with a cell receptor and, subsequently, the delivery of the virus genome into the cell. Individual binding sites on haemagglutinin bind host cell receptors weakly, but multiple interactions can result in a very high binding strength when the virus binds to cells carrying preferred receptor. This is what determines its affinity for a particular host species. 

Led by Steve Gamblin and John McCauley, the NIMR team studied how strongly the H7N9 avian virus isolated from infected humans bound to models of human and bird receptors. 

Their results showed that, although the human H7N9 virus had significantly higher affinity for the human receptor than an H7 haemagglutinin from a typical bird flu virus, it retained stronger binding to the bird receptor, as is characteristic of bird viruses. In comparison, past pandemic flu viruses have shown stronger binding preference for human than bird receptors. 

However the sequence of the haemagglutinin gene of the H7N9 virus isolated from both humans and birds had features that suggested that it interacts with its receptors in a way that is unusual for a bird flu virus. 

Dr McCauley, Director of NIMR's WHO Influenza Centre, explained: "Our results indicate that the human H7N9 virus has acquired some of the receptor-binding characteristics that are typical of pandemic viruses, but that it retains a preference for avian receptors. This suggests that efficient transmission of the virus between humans might be restricted. 

"The increase in the number of human cases of H7N9 in China has stopped and surveillance of poultry markets has revealed only a small number of affected premises. H7N9 seems to be under control at present. Nevertheless, H7N9 viruses still pose a pandemic threat." 

The paper, Receptor binding by an H7N9 influenza virus from humans, is published in Nature.