The Evolution of a New Flu Outbreak

09 May 2013

Interview with

Dr Colin Russell, Deptartment of Zoology, University of Cambridge

In March, a brand new strain of the influenza or flu virus called H7N9 was detected in China.  In the month since its detection, 100 people have been infected and 1/5 of those have died.  We were joined in the studio by Dr. Colin Russell from the Department of Zoology at the University of Cambridge who's an expert on how viruses like H7N9 can evolve to become serious threats.

Kat - Now, just explain, what is H7N9 and why is it different from previous flu strains?

Colin - So, H7N9 is an influenza A virus that is not fundamentally dissimilar to the H5N1 virus or the bird flu virus that we've been so concerned about over the last 15 years. Now, H7N9 is of particular concern because it's something that we haven't seen infect humans before and prior to March, we hadn't seen this virus in any humans ever. Now, since that time, we've seen 130 humans infected with the virus and of those, approximately 20% of them have died. And so, in these particular circumstances where we have a new influenza virus emerging in the human population, it is of course a serious concern.

Kat - I'm sure all of us know about the massive flu pandemics. Before we come to talk about some of the scary stuff, I just had a question. Why are these flu viruses called H-something, N-something? What do those letters designate?

Colin - Well, all influenza A viruses are called H-something, N-something because influenza viruses are characterised by the proteins that are on the surface of the virus.

So, there are two proteins on the surface of the virus. There's the hemagglutinin protein which gives us the H and the neuraminidase protein which gives us the N. There are 16 known hemagglutinins in birds and 9 known neuraminidases which can give us a tremendous number of combinations of viruses that could cause infections in humans.

But so far, we've only seen H1N1, H2N2, and H3N2 cause pandemics in H1N1 Influenza Virushumans. So, the fact that we now have an H7N9 virus causing infections is something new. Now along these lines, we've also seen H5N1 viruses infect humans too, but we've never seen massive human to human spread of any of these viruses other than the H1N1, H2N2, and H3N2 viruses.

Kat - So, this new H7N9, why does it seem to have such a high mortality rate? Why does it kill proportionally more people than some of the other flus?

Colin - Well, as compared to the known cases for H5N1 (bird flu), this H7N9 virus is comparatively less lethal. So, for H5N1, there has been about 600 known cases so far and approximately 50% of those cases have resulted in mortality. Now, in the case of H7N9, we have a situation where we've seen about 130 cases to date and about 20% of those have died. But we don't know that there aren't cases that we don't know about. So, in this particular case, we could just be seeing the tip of the iceberg.

Kat - Where did this virus actually come from because it's originated in birds as bird flu did as well? Where do we think it started and what created it?

Colin - Well, this is a good question and it's one at the tip of everyone's tongue right now because we don't really know where this virus came from. Now, there are some things that we've managed to learn about the virus from analysing its genetic sequences.

So, myself and many others have looked at the genetic sequences of these viruses and we found that these viruses were actually the product of three different influenza viruses. So, influenza viruses, their genes are each coded by individual segments of RNA and they have 8 genes in total. So, the H gene, the hemagglutinin, and the N gene, the neuraminidase account for just 2 of those 8 genes. Now, we know that the H gene came from an H7 virus and that the N gene came from an N9 virus.

But interestingly, the internal proteins, these are the ones that aren't on the surface of the virus, all appeared to have come from an H9N2 virus. Now interestingly, when we look at the genetic relationships among these viruses, we see that the internal proteins, those that came from this H9N2 virus, all are most closely related to viruses that either came from wild birds or from poultry, in the areas around where the original cases emerged. So, we have a good sense in this particular case that we have at least seen the geographic region where the earliest cases have emerged.

Kat - So, there's been some kind of genetic mix and match going on in a bird to make this new virus. So then it sort of spread in birds I guess. How does it get from birds into humans?

Colin - Now, that's a good question as well. So, for influenza viruses, there's a particular term for this. It's called re-assortment because the influenza genes are on each on different segments. The viruses, if they co-infect a host, the genes can get all mixed up or re-assort.

Kat - So mix and match basically.

Colin - Exactly. But in the context of how it gets into humans, in the case of this particular virus, we don't really know where it's coming from. I mean, we certainly suspect that it's coming from birds, but we don't really know.

Now, for H5N1, we have a much better picture of how humans typically get infected and the majority of individuals who've been infected with H5N1 over the last 15 years have been in close proximity to either fowl or domestic poultry.  So, there's a particular story that I like which involves - it depends on who you hear the story from - a Thai duck farmer and this Thai duck farmer lives in his home with his ducks and he has a duck that has flu-like symptoms because frequently, when birds get highly pathogenic, avian influenza viruses, they have the same sort of symptoms that humans have. They cough, they sneeze, they have a runny nose.

Kat - They sit in front of the telly all day and feel terrible.

Colin - Well, if you've got a telly and your duck likes it, there's no reason not to watch it. But basically, this farmer, he sees his duck is suffering and this just isn't agreeable to him and he really wants to help. And of course, you can give a duck a tissue, but you can't make it blow its nose. And so, he decides that he's going to help and he does the only thing he can think of which is, he puts the bird's beak in his mouth and he blows.

Kat - Oh, no!

Colin - Now, this of course causes an evacuation of the bird's nostrils directly into the man's eyes. Now, one of the things that's really interesting about this particular case is that one of the primary reasons that we don't see bird viruses crossing in humans all the time is that bird viruses have a different cell surface receptor that they bind to, apart from what normal human influenza viruses bind to. But interestingly, we have those bird influenza receptors in our lower lungs and in our eyes.

Kat - Oh, my God! So, you basically have to get bird snot into your eyes.

Colin - Well, bird's snot into your eyes would be one way to do it, but otherwise, you need to get the virus deep into your lungs which is not a trivial thing to do.

Kat - You have to be breathing in bird snot basically.

Colin - Or definitely have a very close contact with birds indeed.

Kat - But about this new H7N9, do we know if it can transfer between humans and we know it can go from birds to humans, but what about from human to human because that's when stuff gets really scary?

Colin - Well, that's when it becomes of increasing concern. Right now, there are no known cases of human to human transmission and the Chinese government is doing an extreme amount of work in order to trace all of the contacts of the individuals who have been in close proximity with individuals who have tested positive for the H7N9 virus. And so far, none of these secondary contacts have tested positive for an H7N9 infection which suggests that we haven't seen human to human transmission yet. But that only involves the cases that we know have been - well, that have shown up in hospital.

Kat - So, there may be people out there with it that are just sick and haven't been kind of ticked off on the, "Oh, you've got that." I mean, should we be worried about this, now that we've identified it and we seem to have identified a group of people that have it as a general population and obviously we're in the UK and not in China - Should we be really worried about this or not too worried?

Colin - Well, there's two causes for concern. So one, anytime where we see a new influenza virus that is infecting more than a handful of people, it's a cause for concern because of course in the past, influenza viruses that have crossed from animals into humans have caused pandemics. Now in this particular case, we've seen a fair number of human cases in a relatively short period of time. So of course, that is a cause for concern. Now another cause for concern is that these viruses appear to have mutations that at least in the case of H5N1, could lead to easier transmissibility between humans. Now, that said, we still haven't seen human to human transmission yet, but because these viruses have some of these mutations, there is cause for concern that it might be easier for these viruses to evolve to become transmissible than other influenza viruses that we've seen crossing into humans in the past.

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