Origin of current influenza H1N1 virus

2 March 2009

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

  • http://www.virology.ws profvrr

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

  • Just_another_opinion

    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

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

  • gsgs

    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.

  • Joseph

    To Tabetha – i believe in Jesus, i am sure that “rain, erosion ( see: carlos guevara)”, and all natural phenomena are somehow related to the “supernatural”.
    I have been afflicted by a lung disease, i am vacillating on whether i should get the vaccine or not. Shall i say out loud “Jesus i believe..” and ask my doctor to inject the drug? OK, i will do that right away. And i do not believe in conspiracy theories. The world takes care of itself. It will make the necessary corrections to counteract eventual malevolent “backyard” conspiracy.

    Joseph

  • pkrat

    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?

  • http://www.virology.ws profvrr

    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

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

  • tracy

    when we were promised vaccines in oct 09 and 4 to 5 thousand died as a result ..of that delay. who benefited from those who were infirm and died, because of neglect…… the insurance companies that reluctantly covered them …. now their bottom line looks better?

    When there are men who would murder 90% of humanity to better there place.
    When we can not take care of our own.
    When we live in a production by slavery world
    When the controlling elite think they know whats best…
    When do they know best? When they take and keep taking. When you have less and they have more.?
    Think of the world you want and think of the world they want….
    Who would want a culture of death? When we are by nature a culture of life. What is good what is bad.?
    The corporation lives by rules of money (unnatural) without regard to humanity without care for all.! 6+bn
    Human behavior ?
    When we neglect when we destroy, when we murder

    “The people who are making this world worse don’t take a day off why should I” Bob Marley

  • davidbaer

    Think about this.
    If you really did find a working formula that made you, say $1,000 a week online on average and it kept producing income no matter what, would you want to sell that idea to a bunch of noobs for $47 a pop and expect to retire on the proceeds? No way, man! It does not compute. It does not add up. And it does not make any sense to do that. I certainly don’t go shouting from the rooftops how I make my money online. Hell, I don’t want the competition taking a slice of my pie and neither would anyone who really does make good cash online.
    http://www.onlineuniversalwork.com

  • runtun

    You stated there was an antigenic shift in 1977. How can you be so sure there was a shift in 1977 when the RNA is so similar to that of a 1950 strain?

  • http://www.virology.ws profvrr

    From 1968 only H3N2 viruses circulated in humans. The appearance of
    H1N1 in 1977 therefore constituted a shift because H1N1 viruses had
    circulated since 1957.

  • Masazumi Kawauchi
  • http://www.virology.ws profvrr

    From 1968 only H3N2 viruses circulated in humans. The appearance of
    H1N1 in 1977 therefore constituted a shift because H1N1 viruses had
    circulated since 1957.

  • Anonymous

    Wow what a difference a year or two makes! These guys’ theories look as insane as they actually were at the time. It is just like those Xians who predict the end of the world in a coming year; then you get to gloat when their silliness did not pan out. LOL!! The anti-vaccine crowd are the truest of true religious believers.

  • Anonymous


    I am a researcher ” You mean you Google scary theories and random bits of science that strikes your fancy all day?

  • Anonymous

    Wow, i clicked “like” because you embody the wildest most dramatic* [this is key] post yet. Virology is too boring for you? Then you have the wrong type of imagination for any meaningful science comprehension. Virology can be amazing if you just open your heart to wonder!

  • Anonymous

    I clicked “like” for this one too. So, dramatic!

  • Anonymous

    Excellent theory. this is the one that I myself truly believe in. The planet will go through its normal evolutionary changesInternet
    Marketing Blog

  • Anonymous

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887442/?tool=pubmed
    suggests that the virus was created in ~May 1976 , when labs were
    unusually flu-active because of swine-flu

  • Pingback: [Avian Flu Diary] Pseudo Pandemics And Viral Interlopers | Influenza Virus Mashup

  • CJG

    Actually, from what I know H1N1 Originated from the states from the production of livestock (In particular, pigs). What had happened was you had all these pigs being pumped with steroids to stunt growth, and considering they were all cloned, when they got sick, all of them got sick. So the effect was a crap load of extremely sick and dying pigs. Now Producers decided to start treating the pigs with antibiotics, eventually the pigs became immune to the antibiotics and hence, a new super virus was created and uncontrollable for a while.

  • Yon Zhou

    ugh!!!!

  • Yon Zhou2

    cuz they want a virus that no one but them can immunize

  • drell

    November 1977, I had H1N1. I was 6 years old. I remember 106.2 fever being mentioned by physician to my mother as well as my left lung had fluid in lower lobe. I just remember bad chills, burning eyes and being sick for a long time. I missed a lot of school. I was sick enough that I remember that flu like it happened to me yesterday. I will never forget how sick I felt. In any event, I see the same practice but different physician. November 2010, I discussed that illness with my physician, reviewed my records from 1977. Knowing what it’s like having the flu, I feared becoming ill from vaccination. I just thought it was odd that the seriousness the media and health organizations advise us on influenza, that I never became sick with influenza since 1977. I also told him that over time, I’ve been exposed to people who had an influenza strain (depending on timeframe) but never became ill as well. He told that because I became ill to H1N1 in 1977, I have immunity to most, if not all, identified influenza strains. At least something positive came out of that.