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.
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).