Origin of current influenza H1N1 virus

influenza-oligonucleotide-mapInfluenza viruses of two subtypes, H1N1 and H3N2, have been causing respiratory infections in humans since 1977. Before that year, it was believed that only one human subtype circulated each flu season. How did this unusual situation come about?

Major changes in the surface glycoproteins of influenza virus – called antigenic shift – lead to worldwide epidemics of influenza known as pandemics. There have been six instances of antigenic shift since 1889. In that year, H2N2 viruses circulated, followed by H3N8 in 1900, H1N1 in 1918, H2N2 in 1957, H3N2 in 1968, and H1N1 in 1977. Each pandemic strain carries HA and NA proteins that have been absent in humans for many years, and therefore immunity is either very low or nonexistent.

Influenza viruses of the H3N2 subtype were still circulating in humans in May of 1977 when H1N1 viruses were isolated in China and then Russia. In the winter of 1977-78 the H1N1 viruses caused epidemic infection throughout the Northern Hemisphere. The results of serological tests indicated that the HA and NA glycoproteins of the 1977 H1N1 viruses were very similar to those from viruses of the same subtype which circulated in 1950. Palese’s group compared viral RNA of one 1977 isolate, A/USSR/90/77, with RNA from a virus isolated in 1950. To their surprise, the two viral RNAs were highly related. In contrast, there was less similarity between viral RNAs from the 1977 H1N1 virus and H1N1 viruses that circulated in humans between 1947 and 1956.

Why were the viral genomes of the 1977 H1N1 isolate and the 1950 virus so similar? If the H1N1 viruses had been replicating in an animal host for 27 years, far more genetic differences would have been identified. The authors suggested several possibilities, but only one is compelling:

…it is possible that the 1950 H1N1 influenza virus was truly frozen in nature or elsewhere and that such a strain was only recently introduced into man.

The suggestion is clear: the virus was frozen in a laboratory freezer since 1950, and was released, either by intent or accident, in 1977. This possibility has been denied by Chinese and Russian scientists, but remains to this day the only scientifically plausible explanation.

The close genetic identity between the 1950 and 1977 H1N1 strains was revealed by oligonucleotide mapping. In this technique, purified viral RNA is cleaved with an enzyme, RNAse T1, that cuts the RNA after every G base. The oligonucleotides are labeled at the 5′-end with 32P, separated by two-dimensional gel electrophoresis, and detected by exposing the gel to X-ray film. The oligonucleotides form a pattern (‘fingerprint’, pictured) that can reveal genetic differences between virus isolates. This technique is more sensitive than serologic assays, but only provides information on about 10-15% of the viral RNA. However, the larger oligonucleotides are a representative sample of the entire genome. The authors calculated that there was a minimum of 8 bases changes among the large oligonucleotides of the RNAs of the 1950 and 1977 H1N1 viruses. In contrast, the RNA of the 1977 H1N1 isolate had 38 base changes compared with a 1947 H1N1 isolate.

Oligonucleotide mapping was used to study the genome of the 1977 H1N1 viruses because nucleotide sequencing was not yet in widespread use. Because nucleotide sequencing is now routine, oligonucleotide mapping is no longer used – as scientists like to say, it has been relegated to the museum of obsolete experimental methods.

I was a Ph.D. student in Peter Palese’s laboratory when Katsuhisa Nakajima and Ulrich Desselberger did the work in 1978 that revealed the close identity of the H1N1 strains with isolates from 1950. It revealed to me, for the first time, how an important finding creates enormous excitement in the laboratory and in the scientific community, and how general interest is fueled by the press. The work was accompanied by a News and Views article entitled “Influenza A viruses: shaking out our shibboleths”. I clearly remember Peter Palese asking me if I knew what a shibboleth was. I thought it was one of H.P. Lovecraft’s fictitious creatures.

Katsuhisa Nakajima, Ulrich Desselberger, Peter Palese (1978). Recent human influenza A (H1N1) viruses are closely related genetically to strains isolated in 1950 Nature, 274 (5669), 334-339 DOI: 10.1038/274334a0

Francis A. Ennis (1978). Influenza A viruses: shaking out our shibboleths Nature, 274 (5669), 309-310 DOI: 10.1038/274309b0

Comments on this entry are closed.

  • BNFRMD 28 August 2009, 6:35 pm

    I completely agree with rogerv's assessment of the current H1N1 issue. The pattern of disinformation on the part of governmental agencies replicates that of the emergence of the AIDS virus and also how the virus suspiciously targeted culturally disadvantaged and/or disparaged groups, the inconsistent zoonosis timeline, and how it's emergence coincided with the smallpox and Hepatitis B vaccination campaigns then being implemented within the target populations. Given the above, one should be wary of a government controlled vaccination campaign based on an H1N1 fear. The fact that the devil is truly in the details of a complex science and that the general population has little patience for examining the troubling history behind world governance and strategies of tensions, gives malevolent forces a clear advantage.

  • hadiya varnado 28 September 2009, 4:19 pm

    this is not all info that i needed you guys need to update your site because i learned all this in school i need to know the scientific name for the H1N1 virus and its history not the comparisoion between the h1n1 and the H3N2 ok i need info

  • Ed Wright 5 October 2009, 11:55 pm

    An even better and less offensive name would be Legislative or Government Flu

  • katieRim 12 October 2009, 11:27 am

    With regard to the most recent origin, was it not the US owned, and opeated pig farm in Mexico that was revealed in the Media but never followed up?

  • Blake Connolly 14 October 2009, 11:04 am

    The bible was the best novel ever written.
    Evolution is a theory because ignornat bible types need to have man's timeline laid in front of them like a school lunch line. As we succesfully find these fossils, and prove the exact chain of events, they will no doubt come up with another unprovable concept. That, or they will say “well, ok, yes. It does seem as if all these different steps are very similar, but “GOD” is the one who actually made the last step happen”
    And when you say “All of the brightest minds in the world believe in God as our creator”, you couldn't sound more uninformed.
    Just please let the adults discuss science, and keep the santa, god, easter bunny, vampire stuff seperate

  • yesmiw2035 16 October 2009, 9:43 am

    Must be for CNN

  • Graham 21 October 2009, 7:17 am

    Depopulation should be the highest priority of U.S. foreign policy
    towards the third world – Henry Kissinger

  • katie 22 October 2009, 5:58 am

    I had a friend who had an interesting point of view and I was wondering if you could comment. He seems to think that thia strain of H1N1 did not orginate in the pigs. If it did not start in it's beginning host he thinks it may hve been a government experiment to see how the world would respnd to a global pandemic. Does H1N! have to actually start in the pigs and then transfer to human and then human to human? And could a government actually run some kind of health experiment like this?

  • profvrr 23 October 2009, 3:44 pm

    All the evidence indicates that the 2009 H1N1 virus did originate in
    pigs. It's a new virus with genes from swine, bird, and human hosts.
    The mixing of different viruses probably occurred in pigs but it also
    might have taken place in another host. There are many laboratories
    that can produce genetically modified influenza viruses, but there
    isn't a scientist on the globe who could have known the exact
    combination of human, swine, and avian genes, and the mutations in
    them, that would produce a human pathogen. I realize that many people
    feel that the virus is a government experiments. But there are so many
    different influenza viruses in many different animal species, that it
    would be experimentally impossible to try all the different
    combinations of genes and mutations that would be needed to produce a
    human pathogenic influenza virus.

  • scottsinclair 23 October 2009, 6:18 pm

    This is typical of how we are not in control of our world around us. And I quote, ” The suggestion is clear: the virus was frozen in a laboratory freezer since 1950, and was released, either by intent or accident, in 1977. ” So, in effect, our own stupidity is creating or will eventually create a worldwide epidemic which will kill millions.

  • Name 23 October 2009, 8:47 pm

    The Soviet Union was launching viruses into the upper atmosphere towards Europe and North America, from their island research, I believe an island lab in the now dry Aural sea. This was going to be brought to the attention of the UN, however the Cuban Missile Crisis removed it from the list of important things to do.

    From my understanding, this was never an issue raised to the Soviet Union.

  • Name 23 October 2009, 8:56 pm

    What if the “engineering” was simpler? What if virus material was exposed to various things like radiation, forcing it to mutate? What if they were placed together and in combinations and mutated?

    Seems to me, a ham fisted way could get lucky on making some witch's brew that would infect humans.

    Take bad vial A, and bad vial B, etc. and there you go. Stir it them together and start bombardment.

    Test on subjects of choice.

  • Name 23 October 2009, 9:01 pm

    > When you attempt to inject 60 million to 195 million, or more US citizens, you're going to have a high
    > incident of health related problems just from the thimerosal additive and the Squalene adjuvant al0ne
    > (of which the victims and their families will have no recourse to seek damages in the courts).

    All those sick people might just insist on government health care for a solution?

  • Name 23 October 2009, 9:06 pm

    Firstly, do your homework.

    Darwin ripped off his famous work. (See “A Delicate Arrangement”)

    Also, “The Bible” in current, standard form, is 66 books. Written over several centuries.

    The problem with the “debate” of it in scientific circles, is that on the one hand you have non-scientist believers, and on the other, non-believer scientists. Typically the two sides know little or nothing of the other, and both blather on like two sects at war.

    So, shoving it off just because it seems not scientific, or various believers are not scientists is a bit naive, or uninformed, or possibly just arrogant.

  • Doug Way 23 October 2009, 9:08 pm

    Ask the people at Dugway, maybe they can help you answer that.

  • the_rationalist 24 October 2009, 10:25 pm

    Isn' t this the Mayan prophecy – 2012? You are a nut, ryan. As a PhD grad student in Biochemistry/Immunology, I can say Prof. Racaniello knows his science.

  • Jim Mercer 25 October 2009, 12:40 pm

    Hello Professor.

    Given what you know about Influenza A H1N1, if a Department of Education – in conjunction with a Department of Health and “Mental Hygiene” (NYC as you might guess) – sent a twelve page “Vaccination Consent” form home with your 8-year old daughter, outlining the lovely choices of vaccine options available to you and your daughter, namely, Live Intranasal or Inactivated Injection, which would you choose?

    As expected, towards the end of this masterpiece was a well-crafted paragraph thoughtfully informing me that vaccine injury compensation options and ability to sue are limited by law.

    Noticeably missing was any option to decline the vaccination altogether – which we intend to do. My eight year old is now well-versed in how to say “no”, and to defer “any futher discussion on the matter” to mom and dad. As an aside, our 12-year old daughter had a half dozen friends contract H1N1 earlier in the year. They were sent home, but *all* of them were back in school a week later after bed rest, plenty of fluids, and off-the-shelf flu remedies.

    I'm puzzled (actually, troubled) by the government (and commercial pharma) zeal.

    Again, your view on vaccination options would be appreciated. We see no compelling reason for complimentary doses of Thimerisol and/or Squaline.

    Kind Regards,
    Jim

  • RogerV 25 October 2009, 2:44 pm

    This article is a bit dated, but have heard nothing that would indicate anything that is otherwise – especially in light of Obama now declaring H1N1 a national emergency:

    First Daughters Not Vaccinated Against H1N1
    Posted By Anne Marie Riha On October 8, 2009 @ 3:01 pm In White House
    http://whitehouse.blogs.foxnews.com/2009/10/08/

  • RogerV 25 October 2009, 2:47 pm

    The appearance of this report over in Germany created a bit of a stir there couple weeks back:

    German army gets special swine flu vaccine without controversial additives given to general public
    Published on 10-13-2009
    http://www.blacklistednews.com/?news_id=5925

  • Hector 26 October 2009, 2:39 pm

    Of all the theories I have read, this is the one that I myself truly believe in. The planet will go through its normal evolutionary changes. The problem is, we have gotten too smart to accept that, so we try to make excuses for what is inevitable which is the growth and normal changes of the planet. Face it, we weren't the first ones on this planet.

  • profvrr 27 October 2009, 10:45 am

    Your estimate is more like a guess. On what is it based? Scientists are not chicken; they prefer to use scientific method to test hypotheses. This problem is not testable given the enormous number of viruses and hosts.

  • profvrr 27 October 2009, 10:48 am

    The virus emerged initially in China and Russia, so it's highly unlikely to have come from the US. No conspiracy or germ warfare theories, please.

  • profvrr 27 October 2009, 10:52 am

    It is your choice whether to immunize you or your children against 2009 H1N1 influenza. There is no squalene in the US vaccine, and you can request the thimerisal-free, single dose version of the vaccine. Children appear to be at high risk for H1N1 influenza this year; do you wish to expose them to that risk? Deciding whether to immunize is always a matter of balancing the risks and benefits. In my view the risks of contracting fatal influenza far outweigh possible side effects of the vaccine. Then there is the fact that the more who are immunized, the less the virus will be able to spread. It requires a bit of altruistic behavior.

  • profvrr 27 October 2009, 10:54 am

    The article is dated? Of course it is – it describes the emergence of an influenza virus in 1977. It has nothing to do with the 2009 swine-origin influenza virus. As for the first daughters – they are certainly part of the at-risk pediatric population and I would be surprised if they did not eventually receive the vaccine. Here at the medical center we are technically all at risk yet no H1N1 vaccine has yet come our way.

  • Christine P 27 October 2009, 12:51 pm

    Why is it that pigs are infected with all these different types of influenza? Could any of this have to do with poor care and unsanitary living conditions of the animals. Could they be getting sick from living in filth, having open wounds that become infected, abuse, or neglect? Living in disgustingly horrible living conditions and getting sick, then being left untreated. Could that be the cause of this influenza? Where would the original infected pig get the virus from? I guess I really want to know if this could have anything to do with animal abuse and neglect? Maybe one pig died and its corpse became infected and infected the other pigs, which then infected the farmer, is this possible?

  • profvrr 27 October 2009, 1:50 pm

    And now the NY Times reports that the First Daughters have received their 2009 H1N1 vaccine: http://bit.ly/1eTpgK

  • profvrr 27 October 2009, 2:28 pm

    It's simply not a matter of mixing three or four different viruses together and seeing what comes out. This has been happening in pigs for years and it took from 1918 to 2009 for the right combination of genes and mutations to produce a virus to infect humans. This cannot be replicated in the laboratory.

  • profvrr 27 October 2009, 2:31 pm

    The theory on why pigs are infected with different types of influenza virus – mainly avian and human – is that the respiratory tract of the pig has receptors for both types of virus. It has nothing to do with 'living in filth' or unsanitary living conditions. Influenza virus entered pigs in 1918 – probably when an infected human gave the virus to a pig on a farm – and has been in pigs ever since, transmitted not only among pigs raised for food, but also among feral pigs. The virus is transmitted in the same way as it is among humans – mainly by respiratory aerosol, some contact.

  • RogerV 27 October 2009, 11:28 pm

    Well, thankfully in Aug. 2008 Baxter was awarded patent US 20090060950A1, just in time to be licensed to five or so companies that are now manufacturing it for the March/April 2009 outbreak of H1N1.

    So if it took from 1918 to 2009 for the current H1N1 pandemic to show up on the scene, evidently a benevolent hidden hand provided for a patented vaccine to be developed just in the nick of time for this 2009 emergence. Aren't we the most lucky folks in the universe to have such fortuitous coincidences fall in our laps like this?

    Sort of reminds me of how a visa of one of the 9-11 perpetrators was found unscathed in the rubble of the WTC twin towers. It's always fascinating how the major historical crisis of our era are accompanied by these miraculous occurrences.

  • Jess 28 October 2009, 4:56 pm

    What I would like to know is how it hit so fast so hard. I live in Quebec which is obviously nowhere near Mexico and in a matter of a week the H1N1 Virus is all over the place. apparently like 28 people in Montreal have died. I'm not exactly sure if that's just this week or what but it's quite disturbing. I just ran into a friend out on the street and his wife and 2 daughters have it. it's kind of nerve racking cuz I myself have a wife and 2 kids, a 1 yo and a 5 yo. In addition to all that biblical bull crap which keeps popping up….no god would kill the innocent.

  • profvrr 29 October 2009, 3:19 pm

    The rapid spread of 2009 H1N1 virus can be explained in at least two ways: most of the population has no immunity to this new strain, and airline travel is very efficient at bringing viruses around the globe.

  • RogerV 31 October 2009, 12:30 pm

    Satinder Singh looks to have copied this article near verbatim from this posting:

    Startling New Evidence That The 'Swine Flu' Pandemic Is Man-Made
    Novartis Patent Detailed And Mass Murder Charged
    By A. True Ott, PhD, ND
    7-26-9
    http://rense.com/general86/manmd.htm

  • Bear 31 October 2009, 1:42 pm

    If russia or china released the H1N1 virus…. can they be held accountable for the spread and cost of vaccine ?

  • JuJo 2 November 2009, 6:47 am

    But where did it originate from???

  • jbones 4 November 2009, 10:10 pm

    Well Roger what a breath of fresh air you are.
    Baxter gets a patent for a virus six months before H1N1 actually rears its ugly head in a moutainous city in Mexico on the same day the U.S. Commander in Chief pays a visit.

    Maybe it is the same miraculous coincidence that the previous C in C has a brother Marvin who's security company retire their position a couple of days before a couple of aircraft (from airlines also under the security of Marvin's company) smack into the WTC spewing lethal kerosene that can melt steel causing the buildings to fall down. Wow! I wish my Kero-Sun heater could do that.
    I always found when trying to melt steel that you needed Oxygen (and plentyof it) to get a fuel hot enough to accomplish that. I wonder how you find that much oxygen that would keep spewing black smoke for some time before lethally beginning a trek through a hermaticlly sealed shaft to the basement. And the pasport visa survived.

    My, my, how I love coincidences.

    Cheers

  • lilaaron 9 November 2009, 10:40 am

    will someone tell me wat is a origin h1n1 will someone please.. im at skool and i need dis answer..

  • Woop 11 November 2009, 4:34 am

    I checked out this patent. It's not a “swine flu vaccine” patent as some people have claimed. It's just a patent for another way of developing a viral vaccine. I have no idea how common this is, so I can't comment too deeply on its significance, but it doesn't seem sinister.

  • Woop 11 November 2009, 4:34 am

    I checked out this patent. It's not a “swine flu vaccine” patent as some people have claimed. It's just a patent for another way of developing a viral vaccine. I have no idea how common this is, so I can't comment too deeply on its significance, but it doesn't seem sinister.

  • Woop 11 November 2009, 4:36 am

    Who said the steel needed to melt for the building to collapse? I'm pretty sure a steel rod will break long before it melts.

  • Dee 12 November 2009, 10:32 am

    umm, just a thought from a common lay person.. WE'RE ALL GOING TO DIE ANYWAY….!!!

  • profvrr 12 November 2009, 10:34 am

    That's true, but wouldn't you rather live for 70-80 years rather than 30?

  • mollymcphee 14 November 2009, 5:30 pm

    H1N1 Spanish influenza 1918…yes WE HAVE SEEN IT BEFORE

  • John Charlton 25 November 2009, 9:42 pm

    Dr. Racaniello,

    What is your reaction to the recent article in Virology, on the origin of the Swine Flu

    http://www.virologyj.com/content/6/1/207

    by Drs. Gibbs & company….

  • profvrr 30 November 2009, 2:41 pm

    It's an interesting idea, certainly with merit. I plan to write a post
    on that article this week.

  • Just_another_opinion 9 December 2009, 9:04 pm

    I agree, I had symptoms and was sick and had to cancel a flight to Mexico, from California, two weeks prior to the announcement of the swine flu, later named H1N1, blaming Mexico as the place of origin, which I doubt very much is the case. I would pick the US, and California before Mexico as the place of origin and Asia could be the source country; having traveled around the world for over 40 years, and I specifically started traveling to Mexico in the early 60's, and to China in the late 70's, traveling back and forth numerous times, conducting business in both countries, leads me to believe Mexico is probably a scape coat situation, just a guess…

    My question is; How do you know it is NOT a “Mexico type”strain? If that is the case, then from what I have read in this blog, it may have been a stored strain and was accidently released or whatever from a lab.

    Note: There are journals written that indicate that the US gov released a swine flu strain in the 70's or early 80's as I recall, to learn how long it would take the strain to travel across the States, testing it on US citizens for biological warefare data, protected under national security guises, which basically means that US citizens can be used a guinea pigs for national security protections and causes.

    It seems more plausible to be an old strain, stored in a lab, that was released; when, how, for what reason, who knows and who cares, its here, so avoid contact with anyone that is sick.

  • gsgs 10 December 2009, 4:27 am

    lots of seasonal flu in California at that time. First confirmed mexflu is from
    February,24 in Potosi

  • gsgs 10 December 2009, 4:33 am

    your estimate about my estimate is just a guess. I based it on what I read about the subject.
    If scientists give no estimates (“guesses”) then we have to rely on the estimates
    from the journalists and actuaries. Do you want that ?
    What for do we have the scientists if not for estimating the future ?
    If any such estimates were useless then so were all the writings an
    papers about it. Simple logic.

  • pkrat 22 December 2009, 10:07 am

    Why wud u get a vaccine for a rapidly Mutating Virus? its not going to do any good once the mutation occurs, So either then u will need another vaccine, or the vaccine was never intended to help in the first place. Can anyone explain this?

  • profvrr 22 December 2009, 10:59 am

    Influenza vaccine is typically effective for 1-2 seasons, after which
    genetic drift has sufficiently changed the virus so a new vaccine must
    be formulated. So the answer is, we use vaccines even against variable
    viruses such as influenza because they do protect from disease for a
    year or two.

  • Swine Gal 6 January 2010, 12:56 pm

    I would like to know the economy effects of the H1N1 Epidemic of 1977-1978.
    Thank you,
    Swine Gal