How influenza evolves
Mind your H’s and N’s
Flu’s success owes much to its genetic mutability
BOTH “mini-epidemics” of seasonal flu, which happen most years, and much larger pandemics, of which 1918’s was the worst example, are the result of an arms race between the influenza virus and the immune systems of the animals it infects. Here’s how it works.
Type A flu viruses—those which cause pandemics, and also most seasonal flu, have two important surface proteins, haemagglutinin (H) and neuraminidase (N). Haemagglutinin helps the virus invade a target cell. Neuraminidase helps new virus particles break out of that cell. These two proteins are also antigens, meaning that they are parts of a virus that may be recognised and reacted to by the immune system.
But the process by which a flu virus hijacks a host cell’s molecular machinery in order to reproduce itself cuts out of the loop what are known as proofreading enzymes. The virus’s genetic material is thus copied with low fidelity, meaning proteins derived from it vary considerably in detail. That variability generates antigens which immune systems do not always recognise and react to immediately. Each year’s seasonal virus is therefore slightly different, and thus requires an updated vaccine—which is not true for most antiviral vaccinations.
Pandemic viruses represent bigger shifts in this process. These create antigens sufficiently novel that have been given numbers by virologists (eg, N1, H3). Many hosts’ defences are unprepared for such big shifts, which happen, on average, three or four times a century. The 1918 pandemic was caused by a strain with a version of haemagglutinin called H1 and a version of neuraminidase called N1. The two subsequent flu pandemics of the 20th century, in 1957 and 1968, were caused by viruses carrying H2 and H3 antigens respectively, in combination with N2.
Much of this mutating goes on outside human beings. Influenza is primarily an infection of birds, especially waterfowl. In these animals the virus infects the digestive system rather than the respiratory tract, usually without producing signs of malaise. Occasionally a bird-flu strain arises with molecular tools that enable it to infect people—the H5N1 and H7N9 strains are currently worrying disease-surveillance experts.
The virus sometimes jumps directly from a bird (often a chicken) to a person, but more usually passes via a pig. The cells lining bird guts and human lungs are built differently, meaning that the virus needs different sets of tools to invade them. Pig-lung cells, sharing properties of both, act as intermediaries in which the virus can adapt from one to the other. Even after it has infected a human being, though, a virus cannot go on to cause a pandemic unless it also acquires the ability to pass easily between people. Fortunately, this is something H5N1 and H7N9 have yet to do.