Monday, 21 November 2011

Much A-Flu About Nothing (Post 1 of 2)

Everyone knows of flu, or to give it its full name, influenza. For most people it’s nothing more than a passing illness characterised by symptoms such as fever, fatigue, coughing, sneezing, aches and pains. However, for some people, it can be a much more serious disease, with estimates from the World Health Organisation believing it to cause 250,000 to 500,000 deaths a year. Those people at the highest risk have probably already been contacted with regard to receiving the flu vaccine, which is an annual occurrence around this time of year (in the northern hemisphere). What I’d like to talk to you about in this blog is what flu is and why every couple of years there seems to be a huge scare about a pandemic outbreak, the most recent of these being Bird Flu and Swine Flu. I don’t want this to be a scare-mongering blog about how there could be a pandemic flu outbreak that could kill us all (as the papers like to report it) but just to help people understand what is going on next time there are reports of a potential outbreak.

First things first; flu is caused by a virus. One of the defining features of viruses is that, unlike bacteria, they are completely unable to replicate without a host, and the aim of any living thing is to replicate. So without something to infect, viruses would just sit there as a ball of DNA, proteins and fats doing nothing. The influenza virus has 3 main hosts, these being humans, pigs and birds. The virus must therefore infect one of these animals, replicate inside their cells and then spread to new hosts. In humans, the virus infects cells in the upper respiratory tract, which is why we cough and sneeze a lot when we have flu.

Now for a bit of virology. A virus is unable to replicate without a host because of the fact that, in general, all a virus consists of is genetic material (either DNA, like us, or RNA) and a particle which transports this material, made up of proteins and fats. This particle is known as an envelope. In this envelope there are proteins, which stick out (see the picture) known as haemagglutinin (HA) and neuraminidase (NA). Both of these have very important roles for the virus. HA allows entry into the cells and without entry the virus cannot live. NA on the other hand allows the virus to leave the cells and spread to more cells. And yes, if you were wondering, these are where names of flu viruses such as H1N1 come from. These notations refer to which distinct type of HA and NA is on the surface of that flu virus. We currently know of 16 HA variants (numbers 1-3 infect humans) and 9 NA variants (only numbers 1 and 2 infect humans).

The last bit of background regards the influenza genome. The genetic material of influenza is RNA and inside each influenza particle there are 8 different segments of RNA. This is like having a jigsaw of 8 different pieces, all of which have different detail to them and all of which are necessary to have the final image. Each of these 8 RNA molecules will produce different proteins that enable the virus to replicate inside host cells and then spread.

Now that we’ve got the background down, things start to get interesting. As long as the flu virus has all 8 of the RNA segments it needs in the genome, it doesn’t care where they all come from. So let us think of a typical human flu virus with its 8 RNA segments. If segments 4 and 5 (for example) are exchanged with a flu virus that infects birds, we have a whole new virus that may be capable of infecting humans. We can take this idea further and include pig viruses as well and get what is known as triple re-assortments, where we form a completely new virus with RNA segments from human, pig and bird viruses. This is what scares virologists and epidemiologists the most.

Most people never get anything worse than a severe cold from flu infection due to the ability of our immune system to fight it off. This system of cells and molecules can detect the flu virus by means of molecules known as antigens. Our immune system is essentially blind and has to fumble around feeling for things it recognises as being an invader before it can destroy them. The main antigens that we use to detect flu are the HA and NA proteins I described earlier. Now let us consider recombination: if a flu virus recombines the segments of its genome which code HA and NA, then there is the potential to produce a flu virus with completely different HA and/or NA which in turn will be completely un-recognisable to our immune system, the system won’t know what that feels like so will ignore it.

Being that this new flu virus has a whole new set of antigens, no-one in a population will have immunity to it, which allows for the very rapid spread of a highly infectious virus. This will start as an epidemic and spread from there to eventually become a pandemic. A small caveat to this is that it is not always necessary for there to be recombination for a pandemic to occur; sometimes flu viruses which infect animals can simply mutate to aquire the ability to infect humans instead, bringing with them a whole new set of antigens.

So the question is: what, potentially, can the consequences of all this be? And why are we so scared? In the next blog we will look in detail at one of the worst global pandemics in history and also at two more recent examples of a pandemic and near pandemic that never really lived up to the hype, and why they didn’t. So come back soon to learn more…

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