The Norwegian Institute of Public Health is reporting sporadic occurrences of a mutation in a portion of the flu virus that is involved with the process by which it attaches to cells. I use the word "sporadic" because at this point there is no evidence that the cases where the genetic change has been found are epidemiologically linked. Therefore we don't see it spreading from person to person but rather arising in people after they have been infected. At least that's how it appears from reports, but we have only preliminary information at this point. According to WHO, the mutation has been seen before, again sporadically and as early as April, in Brazil, China, Japan, Mexico, Ukraine, and the US. Should we be worried about it?
For me that's not exactly the right question because I worry about everything when it comes to influenza. Just like auto accidents, flu infections come in a huge range of severity from barely visible scratches to fender benders to whip lash to multiple disabling injury to death. I don't take the potential of being hit by a car lightly either. Any instance could kill me or someone I love. The right question is whether I am especially worried about this report. Not yet. As more information becomes available I might get more worried or dismiss it entirely as the kind of change we see when a virus isn't very fastidious about how it reproduces. Because it's not about the specific mutation but about the biology and we don't know how to read the biology from the genetic sequence. Much of what we thought was important with respect to transmissibility or virulence or something else has been shown wrong by the virus itself. Every time we think we have a fix on it, it shows us otherwise. Here's what we wrote two months ago when the Dutch found the E627K mutation in PB2 in one of their isolates:
Even though this virus has been described as relatively stable genetically, individual viruses, even within the same patient, often have small differences in the thousands of letters that make up their genetic code. Influenza A virus is a very sloppy reproducer, and while its only objective in life is to make a copy of itself it often does single task very badly. But it's like the guy who was asked how he could sell his gasoline for a penny less than he paid for it, his answer was, "volume." The flu virus makes so many copies of itself when it infects a host cell that it can afford to make a lot of mistakes. Usually those mistakes are disastrous for the copy and it doesn't replicate any more. Very many of the little mistakes are just little mistakes and don't affect the virus at all. And some of them turn out to be good for the virus and possibly bad for the host in that they allow the virus to replicate faster, infect more and different kinds of cells and increase its ability to transmit from one host organism to another (transmissibility). (Effect Measure, October 1, 2009)
The Dutch mutation was thought to strongly determine whether the virus would be more avian or more human, but swine flu went ahead and infected humans all over the globe with the version thought to be more avian. It apparently hadn't read that it needed this mutation to be adapted to humans and so far E627K hasn't taken root. In the case of the Norwegian mutation (D225G) we don't even have a theory about its significance, although it is in the part of the virus that binds to the host cell for entry.
What are the possibilities? This change isn't likely to make this virus more transmissible. It's already transmissible as hell and doesn't need any help in that department. It isn't in the part of the viral protein that the vaccine is directed against, so I doubt it would make the vaccine unusable. The same is true for antiviral activity, even though resistance to antivirals is likely to emerge via other mutations. CDC and the UK are both reporting some instances of Tamiflu resistant virus spreading from person to person. What the virus means for virulence, however, is unknown. The Norwegians speculated it could make the virus more prone to infect the lower respiratory tract but they are speculating. That would seem to be the major concern at the moment but there isn't much to go on.
Having said these somewhat reassuring things, however, I don't want anyone to be reassured. We are in the early stages of a pandemic with a dangerous virus and there is just too much we don't know to be able to be either alarmed or reassured by any particular piece of news. In our view focussing on particular mutations is not especially valuable in the current state of our knowledge. The flu virus isn't especially big but it is still too complicated for us to understand. There are eight genetic segments, each of which undergoes both mutation and reassortment, i.e., some of the internal segments mix and match between viruses and new combinations emerge.
The best way to think about this is that these eight functional segments act as a team. When one member of the team acquires a new skill, the value of that skill depends upon how the whole team works together. Sometimes a superstar isn't the best thing, but a group of less talented but smoothly working players is what is needed. But there's no rule about this. Some years teams make it to the Superbowl because of having one or two outstanding athletes ("stars") while other years it's the team that makes the fewest mistakes and works best together that wins out. We don't know how to predict this for sports teams, an easier problem than for the team of eight in the influenza virus.
The mutation is being widely reported to be D222G (this is H1 numbering; it is 225 in H3 numbering). What this designation means is that in the spikes of hemagglutinin protein on the outside of the virus (parts of which elicit the primary immune response), the amino acid 222 places in from one end has changed from "D" (aspartate) to "G" (glycine). Does this change in one of the team members make the virus operate much better? Does it change the biology in any way, and if so, in what way. We don't know. And what does "better" mean in terms of the virus? We aren't sure of that either. The bottom line for the virus is that it make more copies of itself, but the factors that allow it to do that (e.g., should it become more virulent or less virulent?) are unpredictable and largely unknown. This is what this statement by WHO means:
The significance of the mutation is being assessed by scientists in the WHO network of influenza laboratories. Changes in viruses at the genetic level need to be constantly monitored. However, the significance of these changes is difficult to assess. Many mutations do not alter any important features of the virus or the illness it causes. For this reason, WHO also uses clinical and epidemiological data when making risk assessments.
In other words, when it comes to genetic sequences, it's not what the sequence says but what the sequence does. And we can only know that by watching. This is the first time we have watched a pandemic unfold in real time and we still don't know how to interpret many of the things we are seeing.
The virus will tell us, eventually. We'll just have to stay tuned.
Addendum: For those with a more technical interest, there is a good rundown of previous experience with this mutation over at the Flu Wiki Forum by SusanCC here. Recommended. If you want to know more about the Stevens paper she cites, we posted on it here and the general subject here and here and the complexity of it here.
Hi Revere. Has that particular mutation (222/225?) been found in a somewhat evenly distributed fashion on the spectrum of mild to severe to fatal cases of swine flu? Or has the mutation been more frequently correlated with the severe-to-fatal cases? And, if it is being found in severe and fatal cases, have such cases tended to be those in which autopsied patients exhibit the horrifying, black, mushy lung thing?
Speaking of the nasty black lung thing--you wrote about a Branswell article several months ago that described some Winnipeg doctors who were fairly horrified by the appearance of some swine flu victims' lungs upon autopsy. Do we know if genetic sequencing was done on those particular cases, and if so, do we know if such testing revealed anything peculiar?
melbren: You are really asking if the genetic change is associated with virulence. We don't know. It has been seen in both severe and mild cases but the sampling isn't representative, with severe cases being looked at more closely. There are a lot of open questions, many of which we will eventually have some kind of answer to, but probably not for a couple of years. Science is slow, even when it is moving fast as this science is. It is also underfunded, so there aren't as many hands working on it as there might be if we hadn't been cutting the NIH budget (by flatlining it) for the last many years. Hemorrhagic lungs are seen in seasonal flu, too. It's not specific to swine flu, bird flu or 1918 flu. The main question is whether the pattern is changing. Ask me later (in a few years).
Revere, the folks over at Recombinomics (http://www.recombinomics.com/News/11210901/D225G_Evidence.html) have been comparing the D225G change to 1918 strains pretty frequently (may I say stridently) over their last several reports, but I wonder, similar to what you pointed out above in finding hemorrhagic lungs in seasonal flu, do we know if this type of change was found in the more tepid '57 & '68 pandemics as well?
Okay. I will ask you in a couple of years--as long as the black mushy lung thing hasn't killed me by then.
And as far as funding is concerned--you have to look at the glass as half full, not half empty. Perhaps Americans do not enjoy the benefits borne of adequate funding for infectious disease surveillance and research--but we have other things that matter--like granite counter tops and stainless steel appliances.
Jon: E627K is also found in 1918 but also in seasonal flu but not swine flu. I agree there is a difference in attitude to what individual mutations mean here (and for most flu scientists) and at Recombinomics (a company whose product is based on using genetic sequences to predict things). Only time will tell. In the meantime, we'll keep on doing what we do and Henry will keep on doing what he does.
After paying attention to Niman for years now (following H5N1), I'm reminded of what an economist said of his profession. "Economists have successfully predicted 15 of the past 5 recessions, except for the current one". It's not to say they not have good insights, its just that they may over-estimate their own predictive capabilities.
That said, I would hope lots of resources are available to follow up on this. More testing of for this variant among healthy, mildly ill, dangerously ill, flu deaths, and everyone in between. Given the risks posed by a more deadly version of a highly transmissible flu, it seems well worth extra effort and attention to get some more empirical data.
Let us know when to stock up on canned goods!
"This summer, scientists from the University of Maryland, the Virginia-Maryland Regional College of Veterinary Medicine and the National University of Colombia published the results of their swine flu research on ferrets. (Ferrets are widely used in flu research because they are susceptible to human flu viruses and display some of the same symptoms as people.) The study suggested that swine flu is unlikely to reassort with ordinary seasonal strains and instead is more apt to crowd them out. We can only hope that it will be equally chaste when it comes to bird flu.
But another study, also published this summer, offers reason to worry about bird flu's potential for a sinister tryst with another virus. The research showed that bird flu has the ability to reassort with at least some other strains of flu. A team at the Centers for Disease Control and Prevention in Atlanta confirmed this by simultaneously infecting ferrets with bird flu and a strain of ordinary seasonal flu. When they later tested secretions from the ferrets' noses, the researchers found that they carried new flu strains that contained genetic material from both of the parent strains."
Interesting - 6 months to produce a vaccine with current technology - thats if ~63% of the vaccine companies employees dont die from a superbug - what would +6 months of canned goods, rice, oil and flour look like anyway for a small fam? #shivers
What Henry Niman has had to say in the last couple of days about D225G isn't based solely on sequences. He notes that of the 10 Ukrainian samples sent to Mill Hill two weeks ago, those taken from individuals that had died was where D225G was found. Correlation does not prove causation, but it should not be dismissed out of hand when it presents itself. It seems to me the more appropriate response would be to say "hey, let's take a closer look at that."
And, not to change the subject, but there are vaccine technologies out there today that take significantly less than six months to generate safe and effective product. They're just not the "tried and true," so they're beneath the radar. It's a shame that the bureaucracy has been allowed to squander such a large chunk of our increasingly-scarce resources on stuff anyone who looked carefully would have found reason to suspect didn't have a chance of being ready when needed. Someone appears to have assumed -- ever so conveniently -- that pandemic influenza would follow the schedule set by seasonal influenza. Time would expand to accommodate the work necessary. Right!
Bob: The problem with the argument is that swine flu cases of varying severity have not been representatively sampled, now do we know about host factors. The most severe cases are preferentially sequenced. There were almost certainly many other changes in those viruses, as well, since that's the usual case. The sequences are consensus sequences from an isolate. There is usually a wide range of sequences even within one person.
The issue with vaccine technologies has been discussed here quite a bit, not just this year but for many years. Until the government guaranteed a market, drug companies didn't care much about vaccines. They weren't profitable enough compared to impotence drugs. So the necessary trials for licensing weren't pursued and the Bush and previous administrations left everything to the private sector. Result: no new licensed technologies. It isn't bureaucracy to require evidence of safety and efficacy before giving something to a hundred million healthy people. If you want to change the drug laws to allow that, argue it to Congress. Even now, people are not anxious to get a vaccine they see as untested even though it is thoroughly conventional and has an excellent safety record. That's the real world.
Revere has avoided responding to the Niman materials so, without presuming to speak for him let me note some things I believe have been posted previously respecting Nimanns blog; I followed it a lot in the early h5n1 era and found a generally alarmist undertone even with obstensive smooth language about 'concerns', over the years every time there is 'news' about a potentially dangerous permutation of flu it appears it is pumped for a few days then we move on to the next alarm, I have also read although I don't know it for a fact that he has some commerical axes to grind respecting medical products he was involved with. I don't know Nimann from adam's housecat so I don't know his motivations and I'm not particularly trying to slam him when he is not here to defend himself. What I am saying is that I have followed his material for a lot of years and it looks to move from one alarm to the next all the while using measured language about 'concerns' I still read him (who know maybe he will turn out to be right) but with experience I don't pay as much attention to him as I do Revere.
It seems to me Bob is right in calling for closer attention here. Nimian suggests that this polymorphism is increasing effective at binding in lung tissue. This not only causes this particular virus to accumulate in the lungs at high levels, but also explains why so many false negatives occur in naseopharyngeal samples. This bears on two 'mysteries' of H1N1 you have pointed too and is, in nimianese, 'cause for concern'.
The ferret studies that came out in July (in Science, I think) said something about the new H1N1 virus infecting deeper in the lungs than the seasonal flu virus they compared it to. Does anyone know if the H1N1 isolates used in that study also happened to carry the D222G mutation?
Thanks for the reminders, Eric and E Rivera. Living in an often-snowbound countryside, I've the habit of stocking up for a week or two; this already stuffs one kitchen, so I think 6 months' goods would fill a house. Welcome to the medieval period. Meanwhile, what are we to think of the tamiflu-resistant person-to-person (possibly) clusters in Canada and UK? Possibly more such clusters simply since more flu cases? But that would still mean more chance of some escaping containment, yes?
Ron: Nobody is saying we shouldn't pay attention. But speculation and suggestions are easy. The deep lung cells of interest are the type II pneumocytes and they have avian-like receptors, as does this H1N1. Also with the ferret studies, the swine flu strains used in those studies didn't have this mutation but showed two discordant things: one that this H1N1 could bind deeper in the lungs; but, the other, it was still causing a lot of mild disease in humans, calling into question the ferret model as a general model for virulence. A change in the receptor binding domain alone doesn't seem like something that would be so relevant here because those cells are already avian cells and this change may make them less so, but in any event, to focus on it is to ignore much of what we know: that every mutation occurs in a genetic context and even the genetic context occurs in a host and environmental one and that all are important. To use a football analogy, trying to determine if a team is going to win on Sunday afternoon by noting that they have a new play or one of their players has learned how to block better is probably of only marginal or no value without knowing the other things that make it significant or not.
S. Lakshmi: We discussed the ferret studies in detail here but the bottom line is that they were infected with the original California04 isolate. It did not have the mutation. The question of greater virulence is somewhat clouded by the fact that the ferrets had some immunity to seasonal flu. And while it is true that they could be co-infected with swine flu and a seasonal flu, there was no reassortment (contrary to what others may have said in these comments, I think). The original post linked here also has a link to the paper, which is Open Access.
Paula: Most people expect the virus to acquire transmissible Tamiflu resistance. So far the resistant isolates have been sporadic (with the exception of a probable summer camp transmission and the current cluster at Duke, both in NC, and the Wales cases). But this is another example of focussing on one mutation, H274Y, which confers resistance to Tamiflu, may not be informative. It is likely that you need H274Y and another change or changes to make the sporadic cases into transmissible ones. The resistance won't spread until it is transmissible.
Revere, re the info on necessity of 2+ mutations, thanks. Is it the case that patient-to-patient transmission has been ruled out, then, for the Duke and Wales clusters?
Paula: No, I suspect this is person to person transmission. What we don't know is whether there is more than H274Y involved in Duke. In Wales I think these are immunosuppressed patients (not completely sure of that). So the virus will likely find the right recipe in time, at least that's the expectation. But perhaps not.
I followed it a lot in the early h5n1 era and found a generally alarmist undertone even with obstensive smooth language about 'concerns', over the years every time there is 'news' about a potentially dangerous permutation of flu it appears it is pumped for a few days then we move on to the next alarm
That's my experience as well. Niman's was the first flu site I followed, but it was soon supplanted by Effect Measure, which is a lot more cautious and informative.
I am frankly concerned; in his book THE EPIC HISTORY OF BIOLOGY Anthony Serafini discusses the issue of virulence in transmittable diseases and cautions that seasonal outbreaks (giving organisms some degree of immunity)are no guarantee of safety
I concur with the concerned. This "new" D225G polymorphism was identified in the necroscopy exams from 4 Ukranian patients, the other 6 samples from live patients did not identify this polymorphism. This same D225G polymorphism was found in the 1918 virus and is characterized by invading deep into the lungs, destroying the tissue, and suffocating the patient.
Although unbeknown to the world the Ukraine has been experiencing a medical crisis over the last month.
Judging from the number hospitalized this death toll is low.
This "mutation" has been seen in isolated cases in the US, Mexico and Brazil but appears to be gaining traction and could be the cause for the recent upsurge of deaths in Canada (52 in 48 hours).
Josh: Every one is concerned about pandemic flu. That's not the issue. The issue is what this mutation means and that's what we addressed.
Scrutinizer: The Ukrainian medical crisis is well known, much publicized and we posted on it here. It is not unbeknown. It is notorious. And those numbers are unlikely to be even remotely accurate. There's probably much more swine flu than they have counted, just as in the US (where the percentages are higher than the Ukraine). They made a mess of it. Was that mess the result of a mutation in the virus? No. What part did a virus with that mutation play in making the mess worse? I don't know and neither do you, but the evidence that the mutation was isolated in fatal cases isn't persuasive. There are many reasons why it appears to be that way that don't mean the mutation is related to virulence, among them that severe cases are dramatically oversampled for sequencing or that this mutation is hitch hiking, or that it is just another variant with no special significance for the biology, etc. Jumping to unwarranted conclusions is a way to fall into the abyss. And in this case it won't change anything that is being done, either in the Ukraine, Norway or the US.
You may have been on top of the Ukraine situation but MSM (ie world) certainly hasnt.
It seems absurd to me that "the way things are done" have not been modified to ensure that this polymorphism is not increasing in frequency and lethality. All of these disputes over it being a trend, jumping to conclusions, or cause of concern would be put to rest if a proper number of samples were analysed and disclosed. I think the results as they are indicate further study should be undertaken immediately. It is preposterous how long it took to release the sequences, how few were done, and the lollygagging given what is at stake. Afterall doing these analyses isnt like building the Hadron collider, is it? And the results would be more significant, in my opinion.
scru: Things cannot be done so easily. How do you propose to get a representative sample, across countries, for this mutation? You can't even do it in one country (the Ukraine) because the infrastructure doesn't exist there and it wouldn't be so easy to do in the US, either. We don't have a "list" from which to randomly pick isolates (I'm using the word "list" in the sampling sense of the sample space). There are studies that are easy to imagine but impossible to implement, so we have to make inferences and in this case the info doesn't yet exist to make inferences with any confidence. And because there is so much to do and resources to do it small relative to the number and size of the tasks, devoting a lot of effort to something that won't make a practical difference is relevant. There is a mistaken impression among people who haven't done studies like this that it's just a matter of collecting existing data and counting. It isn't. I do this for a living in another area of epidemiology (chronic diseases) and I can tell you it is very difficult and there are always loose ends sticking out.
Regarding the MSM and the Ukraine, we quote at length from the New York Times in our post here. It was in many other newspapers as well.
You have to remember that the MSM does not exist to inform. They report on what gets viewers/readers/listener to tune in or to pick up - what they can sell to advertisers as eyeballs and earpans.
Quck snips of information to hype can do that, especially if it has to do with sex, celebrity, or FEAR.
Trying to sell the possible Ukraine polymorphisms as the end of the world to an American audience at this point in the storyline is not perceived as a marketable product (although some will jump into the chasm, many are storyline fatigued, and the actual facts are interesting but incomprehensible as a short snip)
The NYT can do it, and probably a few other MSM venues. But few others will even try.
Why would you think that """What this designation means is that in the spikes of hemagglutinin protein on the outside of the virus (parts of which elicit the primary immune response), the amino acid 222 places in from one end has changed from "D" (aspartate) to "G" (glycine)."""
would imply that
"""It isn't in the part of the viral protein that the vaccine is directed against, """
medmatters: Because AFAIK it isn't an epitope.
Revere -- It is that easy.
Instead of 10 samples have 100 taken from the deceased (400 currently) victims randomly around the country and send them to Mill Hill. Within 2 days results are available and can be qualified. Are 4 of the victims exhibiting this D225G? not a big deal. Are 40 or more of the victims exhibiting this D225G? yes it is cause for concern exemplifying a trend.
Save the in depth studies for later.
scru: How do you know that this variant isn't widespread among mild cases, too? That's obviously important if you think this is correlated with virulence. I just added an Addendum to the post as a guide to the issues here. SusanCC's piece over at FluWiki Forum is very pertinent and I provided some links from here as a guide if you want to know more about the technical aspects.
If it is not an epitope then why does it """elicit the primary immune response""" ?
medmatters: An epitope is the portion of a big molecule, like HA, that is recognized by antibodies. There may be many epitopes (portions) of such a molecule and indeed HA has a number. But AFAIK this part of the RBD isn't among them. So antibodies are directed against portions of this viral protein (hence my language) but not that portion. I tried to careful in my use of language, referring to the viral protein HA (as opposed to, say NS or PB2), since it is the HA that the immune system "sees." But it doesn't see all of it. Does that help?
Well boys and girls its also a shocker to find that over 22,000 of the infected are healthcare workers. Other little birds told me that 400 doses of vax were sent in there to see it if would slow/stop this strain thats running. Out of the recipients which I can guarantee you were not the rank and file joe slobs on the street, 212 got sick. They may have already been infected but it would appear that there isnt a lot of help there by using the vax. They say its still effective, but they are using the same stuff in Germany and it doesnt look like its working too well by their numbers. They are using it in Canada and they had 55 deaths in 48 hrs. The Netherlands is a runaway and they have been vaxing for a long time.
If its mutated then the single question is going to have to be answered quickly. Does the vax provide any support or protection?
But as a side note and Revere maybe you can shed a little light here. If it is mutated, how long would it in your estimation take for the drug manufacturers to isolate this new change, make a vax and then go monovalent, or tri-valent with seasonal, the current strain and the possibly newer yet unidentified strain? Or would it likely only be beneficial to the people in Indon/S. America, Africa, Australia due to time to produce it?
Randy: Of course it's "mutated." It's been "mutating" since day one in the first patient. That's what these viruses do. But it isn't antigenically different so far. The match is still excellent, so there is no need to change a vaccine because it has "mutated." If it becomes totally unmatched, it will take another 6 months to make a vaccine to it, but that's not happening. The idea that this virus is unchanged until now is false. It's been changing in all sorts of ways since the outset, most of them bad for the virus. The current one seems, at best, neutral. There is no way to tell except to watch how the virus behaves. It's very hard to compare behaviors in different parts of the world with different populations and health care services (many severely underresourced), environments, etc. So keep your finger off the panic button.
Dr. Niman, who claims that he was banned from posting here, without explanation, has responded to your post in four consecutive postings at the Rhiza Labs Flu Board, beginning at:
Jon: We can confirm Henry was banned here (and many other places). It did not concern scientific differences. The reveres discussed it at the time and made a collective and unanimous decision not to engage him further. We are holding to it.
I have no dog in this fight as they say, but having posted and read in various locations over the years, I gotta say that "board wars" rarely go well. Snark and ad hominem usually become the major commodity traded. It may not be my place but I'd discourage anyone who regularly follows here from engaging in anything other than clear discussion of facts if they feel the need to engage in any way at all. We all have better and more important things to do with our lives than get pulled into any pissing matches.
Just sayin' is all ...
I'd argue the flu deaths up here in Canada are not evidence the vaccine is ineffective, as the majority of those deaths would be in individuals who got sick before the vaccine was available. We've had a very slow rollout of the vaccine, and in some places very high levels of ILIs.
We only started vaccinating the general population (not high risk) in Ottawa last Thursday, and lineups are still the norm.
This isn't about "board wars," Don, it's about the Reveres banning a great man from this board, and defaming him thereby.
In protest I will not post here anymore and will remove the link to this site from my own.
> Of course it's "mutated." It's been "mutating" since day one
> in the first patient. That's what these viruses do.
> It's been changing in all sorts of ways since the outset,
Yes, that's what flu viruses do all the time.
But then how does this constantly ongoing genetic drift over years and decades of flu evolution apparently never lead to more dangerous variants of the seasonal flu ?
Jon: Yes, it's about destructive behavior, not just here but many other places that have taken the same action we have. Since we can't post on Henry's site, by your logic he is defaming us. Pardon me if I don't understand your "logic." We don't consider ourselves defamed by not having the privilege of posting on his site. That is his right to decide, not ours. We never like to lose a reader but that's a decision for you to make. We wish you good luck. This is a difficult subject we are all trying to understand as well as we can and we all have to decide how to weigh information and provide a forum (or not) for discussion. We continue to list Henry's site on our blogroll so others can read what he says on his own platform which is easily and freely accessible. He doesn't need us.
h1n1_watcher: The virus is not the only player. There is the host and the environment, and the virus itself has no interest in anything but making copies of itself. If that means being dangerous to its host, those variants will be favored. If it means that being less dangerous in some circumstances (because it is more transmissible, say), those will be favored. But the dynamics of all this are still too complicated for us to figure them out, certainly not from just looking at the sequence.
revere, thanks, my main point was that mutations on the HA molecule would tend to have a high likelihood of being important antigenically and thus to possibly evade current vaccines as opposed to pb1, pb2 changes etc.... as you know it can be hard to identify their full effect as they can cause 3 dimensional steric changes even in distant parts of the HA structure.. but HA is where the money is on vaccine changes...
>and the virus itself has no interest in anything but making >copies of itself.
Of course. but this is just a description of the general way evolution works.
My point was something more subtle: If the variability driven by genetic drift of (ordinary seasonal) flu viruses is so large that we have to match this "fast moving target" with a completely new vaccine every year then how does it come that this wide genetic variability apparently does not "show through" at the level of the phenotype, i.e. the level of biological properties like virulence and pathogenicity.
It rather seems as if, with influenza, there are two different "kinds" of mutations: The first one would be the usual fast moving genetic drift and its "purpose" would be to serve as a means to outsmart the host immune system while at the same time (somehow) the biological functioning of the virus is not affected. (as if there were only "synonymous" kinds of mutations ... i.e. different form but same function.
But of course, in addition to this first kind of "camouflage-mutations" there must also occur "real" mutations that hit the "inner engine" of the virus itself and it would be only this latter kind of mutations that could really lead to a biologically/clinically differently behaving virus.
h1n1_watcher: You are making a more complicated point than genetic drift. Genetic drift refers in actuality to antigenic drift. What you are discussing is usually called viral fitness and we don't have any good ways to judge the genetic correlates of it at the moment (which is part of the point of this post). Whether the virus should become more virulent or less virulent or neither in order to accomplish making copies of itself probably depends on a lot of things we don't know. There is a widespread misapprehension that virulent viruses must moderate their virulence with time to accommodate to the host, but we have pointed out this isn't always true, although it often is (post here. So it can go either way and we don't know which way it will jump (if anywhere).
Re this topic, McNeil in the NYT a couple days ago referred to a British report but gives no citation; does anyone know what it may be?
"Experts still need to see whether the mutation â whose shorthand name in virology is D222G or D225G â is becoming more common, and how often it leads to severe disease, [Fukada] said. . .One isolate from Ukraine with the mutation had changed so that swine flu vaccine probably would not protect against it well, Britainâs national medical laboratory reported Friday."