Chris - Viruses are not actually living, they’re just and infectious bag of genes so in other words they are some kind of coat that surrounds infectious material.  This can be DNA which we’ve all heard of, we’ve all got that, or its genetic relative called RNA.

Viruses are so tiny: a flu virus is about 1/10 thousandths of a millimetre across.  That’s too small for them to have any of the machinery they need to make new viruses inside themselves so they need to hijack a cell to do that.  There are viruses for plants, there are viruses for animals and there are even viruses for bacteria - bacteria can catch a cold too!

The flu virus has receptors which are like viral Velcro on the surface of the virus particle.  They will lock onto a target cells using these chemical receptors on the surface which docks onto the cell surface.  They then go into the cell.  Once they’re in the cell they use it like a factory, they take it over and make it produce thousands or in some cases millions of copies of new viruses which come streaming into the cell.  They infect other cells to make more virus or they escape from the body and infect a new victim.

When they’re damaging cells, when they’re infecting cells they can potentially kill them - that’s called lytic infection.  When they kill a cell that has a consequence for us because if it’s a cell in your airway, for example, it might damage the mucosa (the lining of your airway).  This means you get inflammation, a rather blocked-up, sniffy nose.  Plus, because you’ve got damage to the lining of the nose, you might get a bacterial infection on top so they can cause secondary infections.

Kat - Also something like Ebola. Ebola’s a virus where it just breaks down the tissues of the body.

Chris - Yes, it depends on the tropism.  It depends on what sort of cell the virus targets because if the virus goes  into the cells in your respiratory tract then it can damage the respiratory tract.  Flu can damage the lungs and this can cause respiratory failure.  Other viruses have a tropism towards other tissues.  For example, HIV has a tropism towards cells which have a CD4 chemical marker on them.

Kat - Those are immune cells.

Chris - Those are immune cells and so the virus goes into those cells. It can loiter in the cells for a long time before it actually does infect them but often it can damage the cells and make them dead.  If you lose those cells your immune system is disabled.  There’s a whole host of ways in which the viruses can damage different parts of the body.  When you’re got polio virus this comes out of your intestines, goes into your blood, goes to your spinal cord.  It then invades motor neurons which are the nerves which supply your muscles and the virus grows in the motor neurons, killing them in the process.  This paralyses you.  It depends what sort of cells the virus is targeted at to determine how likely it is to cause damage to that tissue and how likely it is to have consequences that are clinical.

Chris - Cold sores are the herpes virus - this is herpes simplex.  There are two types of herpes simplex: type 1 and type 2.  Cold sores traditionally are caused by type 1 herpes.  This is a virus that gets into your body, usually by the age of 3 most of us have picked it up by kissing a parent.

In the first manifestation it goes into cells in the mouth and throat and infects those cells to amplify the virus many times over and increasing the infectious dose.  The first presentation is you get a sore throat and high temperature; your glands come up around your throat.  It then appears to go away for a long time, some people never see it again.

What actually has happened when you had a sore throat was the virus was also infecting sensory nerve endings that supply your mouth and throat.  These nerve endings then transmit the virus back to the spinal cord or to what’s called the dorsal ganglion which is where the cell body for those nerves lives; adjacent to your spinal cord.  In the case of the head and neck it goes up to the trigeminal ganglion which is underneath your brain.  This is where the virus hangs out just as a small circular piece of DNA for the rest of your life.  If you go to the post mortem room and you study people you’ve died you can find evidence of the virus living in 80% of the population’s nervous system.

Periodically and in response to poorly defined stimuli (these can include menstruation, they can include sunburn and tissue trauma – if you get a cigarette burn this can sometimes make it happen) some signal goes back up the nerve, says to the virus, “you’re threatened, you need to come out.”  It reactivates and the DNA turns on again, makes fresh virus particles inside the cell.  They come back down the nerve cell to a patch of skin that nerve cells supplies, the virus comes out of the nerve, onto the skin, raising the skin cells producing an infectious lesion.  That’s a cold sore and the point of this is the virus uses the cold sore to infect another person - when you kiss someone you’re infectious.  That’s how the virus gets around but the rest of it is hiding inside your nervous system.

When it reactivates in that way it can damage the nerve it’s in and those nerves very often are pain nerve fibres.  They get stimulated by the activation of the virus and that is excruciatingly painful and it can persist for a very long time.

Kat - Presumably this is when you get stories of explorers who go to isolated communities and then all the people get really bad illnesses.

Chris - That’s true and the reason is that isolated populations in distant geographical areas which are, in other words, when we say isolated were cut off from the mainstream viruses circulating and other infections circulating where there were big populations in Europe. Those individuals didn’t have the same selective genetic pressure to have a more powerful immune system. If you compare the number of genes in people who are native American Indians and South Americans had for presenting information from the immune system to itself – so when a cells gets infection it presents various aspects of what it seeing washing round the body to the immune system in these things called HLA genes – well the native populations had far fewer of these than the Europeans did. Viruses that breed in Europe are much more virulent under those circumstances because they have to have all these immune evasion strategies built-in in order to outwit the much more powerful immune presenting abilities of the European population.

Kat - So they were really nasty.

Chris - They tend to be more powerful, yeah. If you take them to a population that are more vulnerable they haven’t seen them before. Therefore there’s no pressure on that population  to evolve these defence mechanisms. Those populations are like a souped-up virus and it’s overkill. They don’t need to be that powerful and it makes people much iller than it would otherwise be.

Earlier on in this programme we talked about how diseases spread from animals into people like the rats giving arena virus-like things to people in South Africa.  It can work two ways because scientists published a paper in Current Biology where they showed that chimpanzees are dying of colds that we give them.  There’s a fairly recently uncovered cold virus called metapneunomvirus that we diagnose quite often in people, in humans.  It causes a heavy cold and if you have children it causes wheeziness.  It tends to be self-limiting and goes away.  When people started studying chimpanzee populations in Africa and noticing that they were periodically getting sick and having mass die-offs they found metapneumovirus.  Maybe the chimps were giving the metapneumovirus to the humans.

Actually, there was in South America a few years ago there was a form of metapneumovirus with a genetic signature in it that was very specific to that strain and this then started cropping up later in Africa. This told researchers that in fact we’re giving our viruses to chimps. When you put our viruses that give us a cold into a chimpanzee very often it can kill it. There’s the evidence that viruses are programmed to cooperate with the immune system of the host they naturally affect. If you put them in a different context they can be much worse because they are over-optimised for that particular host.

Chris - What he’s getting at is that some viruses change bits of themselves like the flu, changes its H genes (haemagglutinin genes) on the surface coat of the virus looks a little bit different.  This is called genetic drift and this is down to genetic mutation when the RNA copies itself it makes mistakes and this translates into a slightly different structure for the virus.  This is useful to the virus because it makes it look different so the immune system struggles to recognise it a second time.

Some bits of the virus do such a crucial job that they can’t afford to change because if they did they would impair themselves.  There are some un-variable bits of the virus that don’t change.  What he’s asking is could we exploit that to make better treatments for viruses?

The answer is yes.

A good example is in flu itself.  There was a recent study that was published in PNAS where researchers looked at the way in which a flu vaccine worked.  Flu vaccines are based on the haemagglutinin coats on the virus.  You make a coat on the virus, put it in a egg, you get some virus shrapnel and you can inject that into people.  If you watch how the flu changes over time a vaccine that works against one type of flu might not work against another.  If you get lots of examples of flu virus, compare the genetically you can find elements of the surface coat of the virus that have never changed over that time.  If you make a vaccine out of that then in the case of the paper I’m referring to these people did it with a DNA vaccine.  They just injected the DNA from that little bit of the virus coat.  That hadn’t changed and it was very effective against a broad repertoire of viruses so that might be a better way of doing it.

Another good example is HIV which has to bind onto CD4 receptors on our immune cells.  If the virus were to mutate that bit of itself too much then it wouldn’t be able to infect anymore because it wouldn’t be able to recognise the target.  Researchers are now looking at ways to specifically target the structure on the virus which the virus keeps very hidden but which doesn’t change in order to block HIV.

Chris - Wherever there is an ecological niche something will spring up to occupy that niche. When you’ve got an opportunity for spread to occur and you’ve got humans coming into close contact – it doesn’t matter if you’re kissing someone and spreading Epstein-Barr virus that causes glandular fever or you’re talking about other viruses and bacteria that can spread sexually – there is an opportunity for spread to occur and you have a certain environment which is coming into contact with another environment. That means there’s an opportunity for anything that can tolerate those environments or exploited to spread. Because you have those opportunities and that contact anything that becomes able to exploit that environment will do so. That’s just nature. If as viruses and bacteria evolve and change to exploit those environments so they become specialised to do just that. If you look at Neisseria meningitides, the bacterium that causes meningitis, it’s got a relative called Neisseria gonorrhoeae. In other words the same kind of family, the same species of bacteria can cause bacteria down there and meningitis up there but if you move one to the other location they can cause a sort of similar infection and similar manifestation in both places. If someone gets Neisseria meningitides down there then instead of meningitis they can get a bit of an infection.

Kat - Do you think we are winning against bugs or they’re winning? It seems to be an evolutionary arms race.

Chris - Ever since life got started there’s been a furious arms race going on with each organism on the planet trying to secure its own patch of turf because there’s only so much energy to go round. There’s only so much chemistry to go round and if you’ve got it someone else hasn’t. As populations increase you will see competition between one group of organisms or one entity trying to rob energy or exploit the system better than anyone else. In order to keep up everyone has to change. It’s a bit like radio station changing to digital. You found people buying very expensive equipment that could make your sound a bit louder than the person who was running the radio station next door. The radio station then bought a bigger box that would make them louder than everyone else. Before you know if=t you’ve got this compression war going on where people are seeking to be louder than everyone else. Now people are saying now we’ve got the audio so loud we’re going to make our station distinctive by being quieter than everyone else. It’s the same with microorganisms. They’re going to change and adapt in order to shift and exploit the circumstances as they exploit themselves. We’re never going to have an end to this arms race.

Kat - Do you think we’re due another massive flu pandemic or Black Death plague?

Chris - History has a habit of repeating itself there’s absolutely no doubt about that. We know that flu pandemics come roughly every 30 or 40 years. There’s no doubt that there will be another one. Whether there will be a major manifestation or not we don’t know because the Earth is a very different place now than it was in the past. We’ve got half a million people airborne in aeroplanes at any instant in time. No city is more than 24 hours from any other city which means that’s less than the incubation period for most infectious diseases. At the same time we have more people on Earth – nearly 7 billion than we’ve ever had before and living in higher density than we’ve ever had before. This is the time, if there’s ever going to be one, that we’re going to see some kind of infectious outbreak.