Protein of the Month

April 2006






Molecule of the Month: Haemagglutinin




ExPASy Protein Spotlight


Bird Flu - Haemagglutinin

By Jennifer McDowall



The importance of wild birds in the transmission of disease has come increasingly to public attention in the past few years, both as carriers of disease pathogens (such as bird flu by waterfowl), and as carriers of infected arthropods (such as Lyme disease-infected ticks).  Migratory birds are a particular focus for disease transmission, much in the same way as people contribute to the spread of disease through increased air travel.  Therefore, a better understanding of the migratory habits of different bird population and the diseases they are subjected to may prove useful in predicting possible future outbreaks, which would be more likely to occur along specific migratory routes, especially at common ‘stop-over points’.  This is especially true for emerging infections diseases that are either newly recognised, or were previously known but are now appearing in new populations, geographical ranges, or changing in infectivity.  Once the disease enters the human population, however, the focus must also include infection control at the human population level to prevent a rapid spread of the disease, as seen with SARS (Severe Acute Respiratory Syndrome) in 2003.

Bird flu refers to avian influenza A viruses (AIV) that are found chiefly in birds, but which can sometimes infect humans, though the risk is low to most people.  These viruses do not normally replicate well in humans, because they are not their natural hosts, and are usually picked up only through direct contact with infected or dead birds.  However, these viruses can undergo genetic reassortment to produce new, more virulent strains with increased infectivity. 


Influenza A Viruses, Evolving New Strains


There are three types of influenza viruses - A, B and C - where only influenza A viruses infect birds, while all three types can infect humans.  Influenza A viruses can be classified into subtypes using two main surface glycoproteins: haemagglutinin (HA) and neuraminidase (NA).  There are 16 known haemagglutinin subtypes, H1-H16, and 9 known neuraminidase subtypes, N1-N9, where all combinations (144) are theoretically possible, though only 103 have been described to date.  However, the frequency of the different subtypes found in AIV strains vary, with H3, H4 and H6 being the most common, H5 and H7 being less frequently observed, and the rest being rare; similarly, N1, N2, N3 and N8 are the most common subtypes isolated.  Examples of influenza A subtypes that have infected humans include H1 (H1N1, H1N2, H3N2), H2 (H2N2, H2N8), H3 (H3N8), H5 (H5N1), H7 (H7N3, H7N7) and H9 (H9N2), although only three subtypes (H1, H2 and H3) have become adapted to the human population.  These subtypes can be further divided into strains, which can have substantial genetic differences, and therefore, substantial differences in infectivity (how well they are transmitted) and virulence (potency of infection).  Wild birds are susceptible to all known strains of influenza A viruses, where most strains cause mild disease (low pathogenicity or LPAI), and a few cause severe illness and even death (high pathogenicity or HPAI).  Whether a virus shows low or high pathogenicity depends partly on which species is infected - for instance, some strains that are highly pathogenic in certain fowl can cause no illness in others.

Influenza A viruses are continually evolving, as are all viruses.  Strains with low pathogenicity can evolve into more virulent strains, and through genetic reassortment with human viral strains, especially those that co-infect pigs, new strains can evolve that have a marked increase in virulence for humans.  It is because of such evolution that people can be re-infected with new influenza strains, since their circulating antibodies made to the previous viral strains may not recognise the new ones. 


Next:  Crossing the Species Barrier