The way in: how influenza viruses infect cells

Why are some influenza viruses transmitted so easily between people while others are still restricted mainly to birds?

One important factor is the structure of polysaccharide molecules on the surface of cells, which affects the viruses’ ability to infect and spread.

People, pigs and poultry have different sugar structures on the surface of their cells

Influenza viruses bind to galactose–sialic acid disaccharides, which can be joined via positions 3 or 6 on galactose’s carbon backbone. The resulting disaccharides differ slightly in their conformations, which affects whether or not they bind to different haemagglutinins:

  • haemagglutinins from avian viruses prefer to stick to α2–3-linked sugars
  • haemagglutinins from human viruses prefer α2–6-linked sugars
  • as pig cells have both forms, they can be infected by both avian and human viruses.

Human, pig and chicken illustrations © Glen McBeth

Influenza viruses bind to galactose–sialic acid disaccharides at the ends of long carbohydrate polymers, but they are sensitive to the way the two sugars are chemically linked together. Some like α2–3 linkages; others prefer α2–6. In humans α2–6 linkages predominate, while birds tend to have more α2–3 linkages.

Pigs have both linkages, so can act as mixing vessels for bird and human viruses.

So far, H5N1 has retained its preference for α2–3 linkages. However, an artificial H5 virus with a preference for α2–6 is viable, so would in theory be able to spread between people. However, H5N1 virus strains able to bind to α2–6 have appeared without triggering person-to-person transmission.

Hence, the switch in receptor specificity is necessary but not sufficient for efficient human transmission – other genetic changes are needed too. Identifying exactly which additional changes are necessary is the key aim of ‘gain of function’ studies converting H5 viruses into forms that can be transmitted between ferrets (a model of human transmission).


About this resource

This resource was first published in ‘Influenza special issue’ in October 2009 and reviewed and updated in January 2015.

Microbiology, Cell biology, Health, infection and disease, Immunology
Influenza special issue
Education levels:
16–19, Continuing professional development