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About viruses and viral disease

Origin of current influenza H1N1 virus

2 March 2009 by Vincent Racaniello

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

Filed Under: Information Tagged With: H1N1, influenza, oligonucleotide map

Reader Interactions

Comments

  1. Tabetha says

    1 May 2009 at 9:39 pm

    If you have H1N1 influenza just say out loud now Jesus I believe and I receive you in my heart please help me. Remember God loves you and if you need more help please please go to leroyjenkins.com it will help you tremendously.

  2. carlos guevara-casas says

    1 May 2009 at 10:06 pm

    Incredible funny! I can’t believe than people in usa think this seriously. Diseases are a natural phenomena, there are not nothing supernatural, magical or religious. It is like rain, erosion, etc

  3. carlos guevara-casas says

    1 May 2009 at 10:06 pm

    Incredible funny! I can’t believe than people in usa think this seriously. Diseases are a natural phenomena, there are not nothing supernatural, magical or religious. It is like rain, erosion, etc

  4. bigpicture says

    3 May 2009 at 9:03 am

    The real infection here is lack of real information driven by a propaganda controlled media pushing us towards a fear generated one world order.

  5. bigpicture says

    3 May 2009 at 9:03 am

    The real infection here is lack of real information driven by a propaganda controlled media pushing us towards a fear generated one world order.

  6. Mikh says

    4 May 2009 at 4:20 am

    Are there any possible circumstances in the future the might lead to such accidental or intended release of such supposed to be dangerous viral strains? How does the global community respond on this matter? It is quite disappointing that the knowledge we gain in research or in scientific investigations get corrupted because of such reasons. I hope they can find a way to this issue. Science is there to preserve life and maintain balance in the natural processes of the world not to alter it for things illogically done. Should this be something of truth, it is not good at all.

  7. Mikh says

    4 May 2009 at 4:20 am

    Are there any possible circumstances in the future the might lead to such accidental or intended release of such supposed to be dangerous viral strains? How does the global community respond on this matter? It is quite disappointing that the knowledge we gain in research or in scientific investigations get corrupted because of such reasons. I hope they can find a way to this issue. Science is there to preserve life and maintain balance in the natural processes of the world not to alter it for things illogically done. Should this be something of truth, it is not good at all.

  8. L Ron Flubird says

    4 May 2009 at 6:48 am

    larry.. Fuck you.
    Do The research you will find the the bible is a made for tv spinoff of the story it was based upon.. Thats right Larry the whole Jesus story hapened about a half dozen times or more before the jesus you know ever came into writing. There is no God its made up to give narrow minded people a moral compass, and pushed down your throat to make you easier to control.. Think for your self.. I don't normaly speak in certainties but hey when in roam right.. “All of the brightest minds in the world believe in God as our creator.” That is a fucking one sided statement if I ever heard one.. I mean fuck come on I can show you millions of the dumbest people in the world who believe in God as our creator.. Just look in the mirror..

    Now reply back about how fucking rude I am or I'm going to hell or you will pray for me…
    Or take the high road and bitch about spelling errors and grammar either way I don't care enough to ever check back..

    If you think there is a god great good for you..
    GOOD FOR YOU.
    Just don't tell everyone else that they are wrong because you believe in a talking snake and we don't have a problem..

    hey larry… Go suck Jesus dick on a plane.

  9. L Ron Flubird says

    4 May 2009 at 6:54 am

    Oh yeah and learn to use the reply button.

  10. Vera says

    4 May 2009 at 11:03 am

    I'm a PGY 2 on INT MED and my program director just brought some article on H1N1 resistance to Oseltamivir from 2007 human viruses. I'm searching for some info to show him that the current virus is different from the HUMAN H1N1causing the “regular” flu in recent years. Am I right on the fact that the “H” and “N” does not specify host, virulence or resistance?

  11. Vera says

    4 May 2009 at 11:03 am

    I'm a PGY 2 on INT MED and my program director just brought some article on H1N1 resistance to Oseltamivir from 2007 human viruses. I'm searching for some info to show him that the current virus is different from the HUMAN H1N1causing the “regular” flu in recent years. Am I right on the fact that the “H” and “N” does not specify host, virulence or resistance?

  12. Jorge says

    7 May 2009 at 2:17 pm

    If RNA sequences has been reconstructed in sections, the final sequence may not be different that the original? Second question: why now, May 2009, there are virtually no cases in underdeveloped countries?

  13. Jorge says

    7 May 2009 at 2:17 pm

    If RNA sequences has been reconstructed in sections, the final sequence may not be different that the original? Second question: why now, May 2009, there are virtually no cases in underdeveloped countries?

  14. sean says

    8 May 2009 at 6:16 pm

    okay, THANK YOU. i'm not even in high school yet so i would not know about the complexity of the viruses or anything like that. all i had about viruses was a little bit in class last year, so i would not know about this. THANK YOU for explaining. this clears up a lot, coming from a credible source. with all of the wackos (conspiracy theorists) on the internet, it is hard to find a credible source of information. thank you again.

  15. sean says

    8 May 2009 at 6:16 pm

    okay, THANK YOU. i'm not even in high school yet so i would not know about the complexity of the viruses or anything like that. all i had about viruses was a little bit in class last year, so i would not know about this. THANK YOU for explaining. this clears up a lot, coming from a credible source. with all of the wackos (conspiracy theorists) on the internet, it is hard to find a credible source of information. thank you again.

  16. profvrr says

    8 May 2009 at 6:30 pm

    Correct, the H and N numbers (like H1N1) do not specify host,
    virulence, or resistance. Those vary independently.

  17. profvrr says

    8 May 2009 at 6:30 pm

    Correct, the H and N numbers (like H1N1) do not specify host,
    virulence, or resistance. Those vary independently.

  18. profvrr says

    8 May 2009 at 6:31 pm

    No cases yet in underdeveloped countries? They are mostly in the
    southern hemisphere, where flu season is just beginning. And travel,
    which brings viruses everywhere, is less extensive in those countries.

  19. profvrr says

    8 May 2009 at 6:31 pm

    No cases yet in underdeveloped countries? They are mostly in the
    southern hemisphere, where flu season is just beginning. And travel,
    which brings viruses everywhere, is less extensive in those countries.

  20. XOTAB says

    11 May 2009 at 7:01 am

    Excuse me professor , with all my respect , Mexico , USA ,China , are not in the southern hemisphere on the contrary on the northern hemisphere , it's my knowledge that biologic
    scientific experts don't know much about geography .
    I respect your opinion greatly as far as the developed of the virus (rna) posible mutations

  21. XOTAB says

    11 May 2009 at 7:01 am

    Excuse me professor , with all my respect , Mexico , USA ,China , are not in the southern hemisphere on the contrary on the northern hemisphere , it's my knowledge that biologic
    scientific experts don't know much about geography .
    I respect your opinion greatly as far as the developed of the virus (rna) posible mutations

  22. profvrr says

    11 May 2009 at 7:07 am

    I didn't say that Mexico, China, and the US are in the southern
    hemisphere. I wrote that most of the underdeveloped countries are in
    the southern hemisphere. I do understand that statement is also not
    accurate. It's really too soon to understand why there aren't more
    cases yet in underdeveloped countries.

  23. profvrr says

    11 May 2009 at 7:07 am

    I didn't say that Mexico, China, and the US are in the southern
    hemisphere. I wrote that most of the underdeveloped countries are in
    the southern hemisphere. I do understand that statement is also not
    accurate. It's really too soon to understand why there aren't more
    cases yet in underdeveloped countries.

  24. XOTAB says

    11 May 2009 at 8:33 am

    OK , Sorry you are right , but it is very interesting , as we aproach to summer in the northern hemisphere , the southern hemisphere is now fall , where flu season is just beginning. Thank you for your respond

    Could it be the mutation virus H1N1 is the result of farms domestic commercials animals like pigs the way it is feeding mechanism and ingredients to promote more rapidly growths and lees fatalities or looses per head of animal like the extensive use of anti-biotics or hormones ?

  25. XOTAB says

    11 May 2009 at 8:33 am

    OK , Sorry you are right , but it is very interesting , as we aproach to summer in the northern hemisphere , the southern hemisphere is now fall , where flu season is just beginning. Thank you for your respond

    Could it be the mutation virus H1N1 is the result of farms domestic commercials animals like pigs the way it is feeding mechanism and ingredients to promote more rapidly growths and lees fatalities or looses per head of animal like the extensive use of anti-biotics or hormones ?

  26. profvrr says

    11 May 2009 at 12:02 pm

    Since 1998 many more human and avian influenza viruses have been
    infected pigs than between 1918-1998. This is undoubtedly a result of
    huge increases in raising pigs and domestic poultry, often near one
    another, and the fact that humans need to work with these animals.
    There is no obvious role for antibiotics and hormones.

  27. profvrr says

    11 May 2009 at 12:02 pm

    Since 1998 many more human and avian influenza viruses have been
    infected pigs than between 1918-1998. This is undoubtedly a result of
    huge increases in raising pigs and domestic poultry, often near one
    another, and the fact that humans need to work with these animals.
    There is no obvious role for antibiotics and hormones.

  28. Giovanni says

    16 May 2009 at 11:42 pm

    Could these flu diseases be man made?

  29. Giovanni says

    16 May 2009 at 11:42 pm

    Could these flu diseases be man made?

  30. Giovanni says

    16 May 2009 at 11:47 pm

    You got that right. Look at the big picture.
    Wonder how many of these diseases are man made.

  31. Giovanni says

    16 May 2009 at 11:47 pm

    You got that right. Look at the big picture.
    Wonder how many of these diseases are man made.

  32. Giovanni says

    16 May 2009 at 11:58 pm

    It would not surprise me one bit that scientists were secretly playing
    around with diseases not knowing what they are spreading and came
    up with the current situation.

  33. Giovanni says

    16 May 2009 at 11:58 pm

    It would not surprise me one bit that scientists were secretly playing
    around with diseases not knowing what they are spreading and came
    up with the current situation.

  34. Giovanni says

    17 May 2009 at 12:10 am

    There are some that think like you Ryan. They are beginning to learn
    that behind all of the secrecy and selected media reporting
    that slowly the very disturbing hidden truths comes out.

  35. Giovanni says

    17 May 2009 at 12:10 am

    There are some that think like you Ryan. They are beginning to learn
    that behind all of the secrecy and selected media reporting
    that slowly the very disturbing hidden truths comes out.

  36. eileen and kathy says

    19 May 2009 at 4:16 pm

    wow thats wow

  37. eileen and kathy says

    19 May 2009 at 4:16 pm

    wow thats wow

  38. farrah says

    24 May 2009 at 10:37 pm

    could it be possible that something that may have been frozen like a mammoth or fossil related to the bird swine species have held on to the original strain of the h1n1 and after unearth and defrost transmit to another species and so on…

    also i heard a possible infection occuring from human to swine of this same virus but havent heard anything else…any news?

    and that it was a possible combo in an egg at the cdc that somehow has gotten misplaced?

  39. farrah says

    24 May 2009 at 10:37 pm

    could it be possible that something that may have been frozen like a mammoth or fossil related to the bird swine species have held on to the original strain of the h1n1 and after unearth and defrost transmit to another species and so on…

    also i heard a possible infection occuring from human to swine of this same virus but havent heard anything else…any news?

    and that it was a possible combo in an egg at the cdc that somehow has gotten misplaced?

  40. ingrid rose dedios says

    27 May 2009 at 7:54 pm

    okier

  41. Cenon says

    28 May 2009 at 6:16 am

    Could anyone answer a question on naming the swine flu? Would it be correct practice to refer to the influenza A(H1N1) virus as simply H1N1? Thanks

  42. Cenon says

    28 May 2009 at 6:16 am

    Could anyone answer a question on naming the swine flu? Would it be correct practice to refer to the influenza A(H1N1) virus as simply H1N1? Thanks

  43. profvrr says

    28 May 2009 at 7:51 am

    The name H1N1 is correct but not specific enough; it could refer to
    last season's H1N1, or the H1N1 of 1918. The proper naming convention
    is: A/location/isolate number/year (subtype). So for the current swine
    like strains, one example would be: A/California/04/2009 (H1N1).

  44. profvrr says

    28 May 2009 at 7:51 am

    The name H1N1 is correct but not specific enough; it could refer to
    last season's H1N1, or the H1N1 of 1918. The proper naming convention
    is: A/location/isolate number/year (subtype). So for the current swine
    like strains, one example would be: A/California/04/2009 (H1N1).

  45. johnny says

    28 May 2009 at 7:15 pm

    Dear profvrr,
    What about this virus resistance to live outside its host? (Is this called virus liability?)
    Is it easy to destroy (just as HIV – a “fragile” but dangerous virus) ?
    Washing hands with alcohol gel is useful at all?
    thanks,
    johnny

  46. johnny says

    28 May 2009 at 7:15 pm

    Dear profvrr,
    What about this virus resistance to live outside its host? (Is this called virus liability?)
    Is it easy to destroy (just as HIV – a “fragile” but dangerous virus) ?
    Washing hands with alcohol gel is useful at all?
    thanks,
    johnny

  47. jolinnah says

    10 June 2009 at 5:39 am

    eow andame ng origin ha!!! kakaloka

  48. Anirudh says

    18 June 2009 at 7:15 am

    Can you just explain me the life cycle of this H1N1(swine flu)?

  49. Anirudh says

    18 June 2009 at 7:15 am

    Can you just explain me the life cycle of this H1N1(swine flu)?

  50. profvrr says

    18 June 2009 at 7:44 am

    I've written a few posts here on virology blog about the life cycle of
    influenza virus. They include attachment of viruses to cells
    (http://bit.ly/7GFd8), entry of virus into cells
    (http://bit.ly/TODQ4), viral RNA synthesis (http://bit.ly/zcVwk),
    assembly (http://bit.ly/EZW2q), and pathogenesis
    (http://bit.ly/kpWBb).

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