Common seasonal flu strain binds human host cells less strongly than a decade ago

26 December 2012

Influenza Virus

Image: The influenza virus that caused the 1968 Hong Kong flu epidemic, magnified approximately 70,000 times.

One of the major types of flu virus circulating today, called H3N2, binds less strongly to its receptors on human host cells than its counterpart 10 years ago, according to new research from the MRC's National Institute for Medical Research (NIMR; now part of the Francis Crick Institute). The finding might provide an explanation for the overall reduction in influenza-like-illness seen by doctors during the past decade.

However, John McCauley, director of the WHO Collaborating Centre for Reference and Research on Influenza at NIMR, asserts that we must nevertheless remain vigilant against this serious disease. By improving understanding of how the virus binds to human host cells, the current research should help improve the development of vaccines against future strains of flu.

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 H3N2, which has been causing flu in humans since 1968, and the H1N1 virus that caused the pandemic in 2009 and is still in circulation.    

Pandemic influenza viruses have their origins in birds or pigs. To become established in humans, the haemagglutinin component of the virus must adapt so it can infect and be passed between humans. It can then easily spread worldwide because there is no immunity to it until enough people have been infected, either through infection or vaccination. After a particular flu virus has become established in humans, the haemagglutinin on its surface can change over time to enable it to keep infecting previously immune populations.

The haemagglutinin is responsible for the flu virus binding to host cells, through interaction with a cell 'receptor', followed by the delivery of the virus's genome to the inside of the cell, where it multiplies. A person's main antibody response is directed against haemagglutinin. 

Teams from across NIMR collaborated using a variety of techniques to study these changes in the ability of H3N2's haemagglutinin, from viruses that have circulated over the past 10 years, to bind to proteins very similar to the human cell receptor - mimicking how well they bind to their receptors in human host cells.

They found that more recent viruses showed significantly different receptor binding properties compared with older viruses. In particular, recent viruses bound less strongly to their receptors - meaning they had 'reduced avidity'. The researchers used a technique called x-ray crystallography to look at the structures of the haemagglutinin bound to its receptors from 2004 and 2005 virus samples. This showed marked differences in the shape of haemagglutinin in the part of the protein that interacts with the receptor, which explained this reduced avidity.

Dr McCauley explained: "It is striking that the reduction in the avidity of influenza A(H3N2) viruses for their cell receptor correlates with a reduction in the overall level of influenza disease that has been seen by GPs over the last 10 years or so. We know that A(H3N2) viruses are still circulating, having survived the A(H1N1) pandemic that emerged in 2009, but they might be causing less severe symptoms than previously."

He added: "Nevertheless, influenza remains a serious threat to public health and global surveillance is undertaken to monitor the evolution of influenza viruses to allow the production of updated vaccines to defend against the threat of influenza. This work provides us with a much clearer understanding of the changes in the properties of the virus over time and this will help us develop improved influenza vaccines."

The paper, Evolution of the receptor binding properties of the influenza A(H3N2) hemagglutinin, was published in Proceedings of the National Academy of Sciences.

  • Influenza, commonly known as flu, is a viral infection that can cause serious complications and even death in some people, particularly those with certain underlying health problems.
  • Flu viruses infect a variety of species, including humans, birds, pigs and horses. When a new virus crosses from a non-human species to humans, the absence of immunity in the human population enables it to spread quickly and cause a pandemic. This happened in 2009 with a flu virus called H1N1 from pigs - the pandemic was consequently named swine flu by the media. It very quickly spread around the globe.  The emergence of the pandemic resulted in the rapid development of a vaccine to control the disease; this vaccine is now included in seasonal flu vaccines worldwide.
  • The H3N2 virus caused a pandemic in 1968 - known as the Hong Kong flu - and has been circulating with seasonal flu strains ever since. In this study, scientists showed that one of the proteins on the surface of H3N2 that binds to human host cells has changed significantly over the past decade, leading to it binding human cells less strongly, and potentially providing an explanation for the lower levels of flu reported by doctors over this period.