EnviroSpin Watch

What on earth does 'H5N1' mean? A simple guide.....

I just love the way that media pundits and news readers are relishing giving out the type of the current avian influenza - 'H5N1'. You can see the relish as their tongues curl around this esoteric bit of science. I wonder how many of them have any idea what it means?

So that doughty readers of 'EnviroSpin' are not left bemused and befuddled, here is an 'EnviroSpin' simple guide to 'H' and 'N' ("No chickening out there!"):

The letters 'H' and 'N' stand for two viral proteins that are essential for the life cycle of an influenza virus. In Influenza A (popularly called 'avian flu'), which infects both mammals (including humans) and birds, we currently know of 16 H antigens (bodies that stimulate an immune response) and 9 N subtypes. But what precisely are 'H' and 'N'?

The 'H' stands for Hemagglutinin (H) or (HA): this is a glycoprotein (a macromolecule comprising a protein and a carbohydrate) found on the surface of an influenza virus. It is shaped like a cylinder (see the picture), and it is responsible for binding the virus to a cell that is being infected via its attachment to sialic acid. Hemagglutinin was so named because it is the protein responsible for the ability of the flu virus to agglutinate red blood cells. It is now recognized as the main virulence factor associated with flu. Types H1, H2, and H3 are characteristic of influenza viruses afflicting humans;

[Upper Right: cylinders of death - a simplified model of the Hemagglutinin molecule: licensed under the GNU (GDFL) Free Documentation License. This is material from the Wikipedia article on the 'Hemagglutinin'.]

The 'N' stands for Neuraminidase (N): this is an enzyme found on the surface of an influenza virus where it exists as a mushroom-shaped structure (see the picture). To date, 9 Neuraminidase subtypes are known, some only being found in poultry. However, the subtypes N1 and N2 are strongly linked to flu epidemics and pandemics in humans. The enzyme promotes the release of progeny viruses from infected cells and helps to prevent the aggregation of viruses. Certain chemical inhibitors, such as zanamivir and oseltamivir ('Tamiflu' - Oseltamivir phosphate), are used to block the action of this enzyme.

[Upper Right: ribbons of death - a ribbon diagram of Neuraminidase. The cave-like formation is present in every neuraminidase enzyme and this is the active site influencing a flu's ability to infect: licensed under the GNU (GDFL) Free Documentation License. This is material from the Wikipedia article on the 'Neuraminidase'. NASA public image.]

Flu strains are therefore named after their characteristic hemagglutinin and neuraminidase surface proteins. For example, H3N2 means that the flu has type-3 Hemagglutinin and subtype-2 Neuraminidase. The numbers refer to the type of protein spike from the virus core. Thus H1N1 really refers to a virus with a Hemagglutinin spike of type 1 and a Neuraminidase spike of subtype 1. [Here are two outstanding pictures showing the 'halo' of rigid projections created by Hemagglutinin and Neuraminidase in the envelope of a flu virion, as seen in negatively-stained virus particles. A virion is a virus before it has entered the cell host; it comprises a package of viral genetic material and is roughly spherical in shape and about 200nm in diameter.]

The specific danger for humans is that, where two different strains of influenza infect the same cell simultaneously, new viruses can form which combine antigens. This is referred to as an antigenic shift. For example, H3N2 + H5N1 may create H5N2. Unfortunately, our immune system then has great difficulty in recognizing and coping with the new strain. Such combinations resulted in the 'Spanish' Flu (H1N1) of 1918 (up to 50 million killed); the Asian Flu (H2N2) of 1957 (I was one of only 3 children left attending class in school); and the Hong Kong Flu (H3N2) of 1968.

Finally, it is important to recognise that there are three different genera of the influenza virus, each identified by antigenic differences in their nucleoprotein and matrix protein:

(a) Influenza A viruses infect mammals and birds ('avian flu');
(b) Influenza B viruses infect only humans;
(c) Influenza C viruses infect only humans.

Type A is by far the most deadly, precisely because it can undergo an antigenic shift, as described above. In general, people are able to develop more effective resistance to B and C, because these only experience slow antigenic drift, so that new forms retain similarities with the previous strains and remain recognizable to the immune system.

To date, the 'H-and-N' classification system applies primarily to Influenza A, with only one H type and one N subtype having been identified for the Influenza B virus.

Further reading: 'H5N1' (Wikipedia, October 2005, to be updated).

And, if you'd like your flu protein etched in glass (great Christmas present?), just try: Luminorum. Crystal clear!

Philip, hoping this helps! Now I deserve a good strong morning coffee.