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

221 thoughts on “Origin of current influenza H1N1 virus”

  1. this may be true that as the influenza consist of 8 segments of genes, the rate of mutation is higher compared to DNA viruses + they are negative RNA using the host to replicate within the cells and may mixed with the pig's gene (expressing the glycoprotein that maybe similar to humans') during reverse transcription to produce negative strain and when the viruses are assembled and bud off from the host cells, it carries that glycoprotein and able to infect human's cells. that's what i think why the influenza from the pig could infect human. Like the Spanish influenza that happened during the WW1, could it be military experiment? kills more people than the bullet! or people trying to manipulate the global economy? where tourism would slow down, food industries (pork meat) also affected thus country that exports and imports might as well being affected. this is just theory to think about.

  2. this may be true that as the influenza consist of 8 segments of genes, the rate of mutation is higher compared to DNA viruses + they are negative RNA using the host to replicate within the cells and may mixed with the pig's gene (expressing the glycoprotein that maybe similar to humans') during reverse transcription to produce negative strain and when the viruses are assembled and bud off from the host cells, it carries that glycoprotein and able to infect human's cells. that's what i think why the influenza from the pig could infect human. Like the Spanish influenza that happened during the WW1, could it be military experiment? kills more people than the bullet! or people trying to manipulate the global economy? where tourism would slow down, food industries (pork meat) also affected thus country that exports and imports might as well being affected. this is just theory to think about.

  3. Good question. We don't yet know the origin of the 2009 H1N1 strain,
    and we might never know. Take any news reports on its origin with a
    grain of salt.

  4. Good question. We don't yet know the origin of the 2009 H1N1 strain,
    and we might never know. Take any news reports on its origin with a
    grain of salt.

  5. profvrr,
    How can you explain the following logic with your scientific knowledge?

    The new H1N1 virus is composed of genetic elements from bird flu, swine flu and human flu spanning three continents and 8 decades. There is no conclusive evidence of the laboratory origins of the H1N1 virus. However, because the virus contains code fragments from many sources the origin of this virus is very suspicious. For example, for this to have been a natural combination of viral fragments, an infected bird from North America would have had to infect pigs in Europe, then be re-infected by those some pigs with an unlikely cross-species mutation that allowed the bird to carry it again, then that bird would have had to fly to Asia and infected pigs there, and those Asian pigs then mutated the virus once again (while preserving the European swine and bird flu elements) to become human transmittable, and then a human would have had to catch that virus from the Asian pigs — in Mexico! – and then spread it to others.

  6. profvrr,
    How can you explain the following logic with your scientific knowledge?

    The new H1N1 virus is composed of genetic elements from bird flu, swine flu and human flu spanning three continents and 8 decades. There is no conclusive evidence of the laboratory origins of the H1N1 virus. However, because the virus contains code fragments from many sources the origin of this virus is very suspicious. For example, for this to have been a natural combination of viral fragments, an infected bird from North America would have had to infect pigs in Europe, then be re-infected by those some pigs with an unlikely cross-species mutation that allowed the bird to carry it again, then that bird would have had to fly to Asia and infected pigs there, and those Asian pigs then mutated the virus once again (while preserving the European swine and bird flu elements) to become human transmittable, and then a human would have had to catch that virus from the Asian pigs — in Mexico! – and then spread it to others.

  7. hi content is good but it would be make better if whole life cycle & other details like how does it formed through fusion of 2 strain (human & swine) ..so & so……

  8. hi content is good but it would be make better if whole life cycle & other details like how does it formed through fusion of 2 strain (human & swine) ..so & so……

  9. joejohnson957

    The reality may come out in a few years, but for now it is still a well kept secret. The true origin of the H1N1, and the “swine” influenza viruses since the mid 1980s is the corporations that manufacture the vaccines. To create the vaccines, they must first culture the virus, and render it inert so that it doesn't give the vaccinated individuals the full blown virus. They mostly now can predict which viral strains will be a problem. This is because while they are culturing the virus, they release it in the populations in a few third world countries where sanitation is not so good, and the virus will spread like wild fire. The WHO then gets everyone excited about a pandemic, and the profits generate themselves for the companies who have the vaccine ready to go. They do slip up once in a while, and another flu virus that is naturally occurring infects more people than their engineered virus, but that just helps them appear legitimate. This flue season fewer than normal numbers of people chose to get the vaccinations, and magically the threat of pandemic is lasting much longer than usual. They are just trying to keep up the fear to sell their stockpile of vaccine that was made before the virus was released into the human/animal population to be spread. Look to those who profit from the vaccines, and you will find the source of the flue.

  10. joejohnson957

    The reality may come out in a few years, but for now it is still a well kept secret. The true origin of the H1N1, and the “swine” influenza viruses since the mid 1980s is the corporations that manufacture the vaccines. To create the vaccines, they must first culture the virus, and render it inert so that it doesn't give the vaccinated individuals the full blown virus. They mostly now can predict which viral strains will be a problem. This is because while they are culturing the virus, they release it in the populations in a few third world countries where sanitation is not so good, and the virus will spread like wild fire. The WHO then gets everyone excited about a pandemic, and the profits generate themselves for the companies who have the vaccine ready to go. They do slip up once in a while, and another flu virus that is naturally occurring infects more people than their engineered virus, but that just helps them appear legitimate. This flue season fewer than normal numbers of people chose to get the vaccinations, and magically the threat of pandemic is lasting much longer than usual. They are just trying to keep up the fear to sell their stockpile of vaccine that was made before the virus was released into the human/animal population to be spread. Look to those who profit from the vaccines, and you will find the source of the flue.

  11. May I remind everyone who subscribes to such theories that there was
    influenza long before there were influenza vaccines.

  12. May I remind everyone who subscribes to such theories that there was
    influenza long before there were influenza vaccines.

  13. joejohnson957

    That is true, however the mutation rate of influenza was much slower for many years before the mid 1980s.? Now that there is major profit in the flue vaccine, the mutation rate is 10 times what it was before.? If you weren't attempting to cover up that fact you would have noticed that my original comment was only on events since the mid 1980s.

  14. joejohnson957

    That is true, however the mutation rate of influenza was much slower for many years before the mid 1980s.? Now that there is major profit in the flue vaccine, the mutation rate is 10 times what it was before.? If you weren't attempting to cover up that fact you would have noticed that my original comment was only on events since the mid 1980s.

  15. profrovigatti

    Prof. Racaniello, this is very interesting and helpful, thanks. What are the chances that the current H1N1 strain will recombine/reassort in the future with the deadly H5N1, potentially creating much more serious problems? I think Rob Webster alluded to something like that in a recent review article: I just hoped this scenario would be quite unlikely.

  16. profrovigatti

    Prof. Racaniello, this is very interesting and helpful, thanks. What are the chances that the current H1N1 strain will recombine/reassort in the future with the deadly H5N1, potentially creating much more serious problems? I think Rob Webster alluded to something like that in a recent review article: I just hoped this scenario would be quite unlikely.

  17. “As was pointed out in TWiV, if someone had made the current H1N1 strain, they would
    have at least included resistance to all antivirals.”

    Have enjoyed your article but have found your line of reasoning as to why the current H1N1 of WHO Pandemic 2009 isn't likely to have been produced in a lab to be overly narrow in perspective.

    Why start with a swine virus and engineer it to cross species to humans? Just start with the 1918 or the 1977 swine virus, which was already capable of transmission amongst humans. (Victims of the 1918 were exhumed in order to get tissue to harvest the 1918 virus from – was a very controversial matter in the Seattle Times at the time because of the University of Washington involvement.)

    Secondly, why do you presume the intent would be to design a laboratory virus that is significantly lethal? (Certainly the current H1N1 pandemic virus is not very lethal at all, as flu virus go.)

    Keep in mind that WHO in June raised to level 6, which kicks into gear pandemic mandatory vaccinations. Now whatever nefarious intent that perpetrators may have can be much more reliably accomplished with a forced injection right into the bloodstream of the target populations. Can't get a better form a transmittal than that.

    All the pharma companies producing the vaccine are being granted liability immunity. The Washington Post reports that thimerosal, which studies have linked to autism, is being used.

    “Some of the vaccine will be stored in multi-dose vials containing thimerosal, an antibacterial additive that contains mercury. But there will also be single-dose syringes without thimerosal, a substance that some assert is harmful to children.”

    Two of those companies, Novartis and GlaxoSmithKline, have reported that they're using the adjuvant Squalene. Squalene was the adjuvant used in the anthrax vaccine administered to troops of the first Gulf War and was strongly correlated to those vets that suffered Gulf War Syndrome health problems.

    Baxter patent US 20090060950A1, on which the vaccines will be based, says “[0057] Suitable adjuvants can be selected from mineral gels, aluminum hydroxide, surface active substances, lysolecithin, pluronic polyols, polyanions or oil emulsions such as water in oil or oil in water, or a combination thereof. Of course the selection of the adjuvant depends on the intended use. E.g. toxicity may depend on the destined subject organism and can vary from no toxicity to high toxicity.”

    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).

    Consider how most of the soldiers getting the anthrax vaccine were in the same young demographic that is being singled out as high priority for this fall's mandatory vaccination: 6 month to 24 year olds. The Gulf War Syndrome was a devastating health problem for those that were afflicted. Consider the enormity of what Squalene adjuvant could do if most of the targeted group is successfully inoculated this fall…

    Myself, I don't think thimerosal and Squalene will be the only issues that come from this mass vaccination program. The military is being prepped to help enforce it and conduct quarantines of cities if necessary – as reported by Fox and CNN. A National Guard put out inquiries looking to recruit individuals that have a suitable background for running interment operations (prisons, etc). Stainless steel bracelets with an embedded smartcard RF chip will be used to identify and verify those that have gotten their vaccination(s). This will be required to get past a check point.

    If only the goal of WHO Pandemic (H1N1) 2009 is to kick a militarized police state into high gear, then the lab engineered H1N1 will have fulfilled its mission.

    The problem with scientist is that they become so narrow in their mental perspectives that they often fail to look at a bigger, holistic picture. I see that over and over again. Brilliant people seem to so easily miss what a military trained mind can routinely calculate.

  18. “As was pointed out in TWiV, if someone had made the current H1N1 strain, they would
    have at least included resistance to all antivirals.”

    Have enjoyed your article but have found your line of reasoning as to why the current H1N1 of WHO Pandemic 2009 isn't likely to have been produced in a lab to be overly narrow in perspective.

    Why start with a swine virus and engineer it to cross species to humans? Just start with the 1918 or the 1977 swine virus, which was already capable of transmission amongst humans. (Victims of the 1918 were exhumed in order to get tissue to harvest the 1918 virus from – was a very controversial matter in the Seattle Times at the time because of the University of Washington involvement.)

    Secondly, why do you presume the intent would be to design a laboratory virus that is significantly lethal? (Certainly the current H1N1 pandemic virus is not very lethal at all, as flu virus go.)

    Keep in mind that WHO in June raised to level 6, which kicks into gear pandemic mandatory vaccinations. Now whatever nefarious intent that perpetrators may have can be much more reliably accomplished with a forced injection right into the bloodstream of the target populations. Can't get a better form a transmittal than that.

    All the pharma companies producing the vaccine are being granted liability immunity. The Washington Post reports that thimerosal, which studies have linked to autism, is being used.

    “Some of the vaccine will be stored in multi-dose vials containing thimerosal, an antibacterial additive that contains mercury. But there will also be single-dose syringes without thimerosal, a substance that some assert is harmful to children.”

    Two of those companies, Novartis and GlaxoSmithKline, have reported that they're using the adjuvant Squalene. Squalene was the adjuvant used in the anthrax vaccine administered to troops of the first Gulf War and was strongly correlated to those vets that suffered Gulf War Syndrome health problems.

    Baxter patent US 20090060950A1, on which the vaccines will be based, says “[0057] Suitable adjuvants can be selected from mineral gels, aluminum hydroxide, surface active substances, lysolecithin, pluronic polyols, polyanions or oil emulsions such as water in oil or oil in water, or a combination thereof. Of course the selection of the adjuvant depends on the intended use. E.g. toxicity may depend on the destined subject organism and can vary from no toxicity to high toxicity.”

    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).

    Consider how most of the soldiers getting the anthrax vaccine were in the same young demographic that is being singled out as high priority for this fall's mandatory vaccination: 6 month to 24 year olds. The Gulf War Syndrome was a devastating health problem for those that were afflicted. Consider the enormity of what Squalene adjuvant could do if most of the targeted group is successfully inoculated this fall…

    Myself, I don't think thimerosal and Squalene will be the only issues that come from this mass vaccination program. The military is being prepped to help enforce it and conduct quarantines of cities if necessary – as reported by Fox and CNN. A National Guard put out inquiries looking to recruit individuals that have a suitable background for running interment operations (prisons, etc). Stainless steel bracelets with an embedded smartcard RF chip will be used to identify and verify those that have gotten their vaccination(s). This will be required to get past a check point.

    If only the goal of WHO Pandemic (H1N1) 2009 is to kick a militarized police state into high gear, then the lab engineered H1N1 will have fulfilled its mission.

    The problem with scientist is that they become so narrow in their mental perspectives that they often fail to look at a bigger, holistic picture. I see that over and over again. Brilliant people seem to so easily miss what a military trained mind can routinely calculate.

  19. The mutation rate, defined as changes in the RNA genome, has always
    been the same for influenza viruses. The rate of antigenic change has
    varied, according to species. For example, in pigs the rate of
    antigenic change was modest from 1918 until the 1980s.

  20. The mutation rate, defined as changes in the RNA genome, has always
    been the same for influenza viruses. The rate of antigenic change has
    varied, according to species. For example, in pigs the rate of
    antigenic change was modest from 1918 until the 1980s.

  21. It's impossible to determine the chance of reassortment between the
    2009 H1N1 and H5N1 viruses. We do know that reassortants between the
    two viruses certainly can occur, and animals can be infected with both
    strains. Whether a reassortant virus will emerge that is able to
    transmit efficiently among humans is anyone's guess. There are no data
    which would allow calculation of the probability of this event.

  22. It's impossible to determine the chance of reassortment between the
    2009 H1N1 and H5N1 viruses. We do know that reassortants between the
    two viruses certainly can occur, and animals can be infected with both
    strains. Whether a reassortant virus will emerge that is able to
    transmit efficiently among humans is anyone's guess. There are no data
    which would allow calculation of the probability of this event.

  23. Very good, BRAVO really! I am a researcher and have heard many takes of this H1N1 virus and although I have taken most accounts with a grain of salt (because of how many) I must say this seems to be the most logical one. Origin relating to the time frame seems practical yet political tide has seemingly taken it too far. The UN declares a level six pandemic in the summer, and I am seeing more license plates labeled DHS government vehicle. One very interesting thing I was discussing with a retired doctor was research on PH levels, Alkalinity, and Cancer that somehow lead to an informative discussion about Colloidal Silver even though it is unrelated. I am no doctor but it has been proven that if used correctly this Colloidal Silver could be used as a measure against such viruses and so far the impact of H1N1 on global population seems to be only 3% making the seasonal flu more deadly. Am I correct in believing that although the topic of H1N1 is extremely interesting because of it's occurrence it may be less of a monster than propaganda and politics make it seem? The question then is, what will prove as the bigger threat? The virus or the governments attempting to contain it? I am interested as to your perspective, please share.

    Yours truly

    polititalk

  24. Very good, BRAVO really! I am a researcher and have heard many takes of this H1N1 virus and although I have taken most accounts with a grain of salt (because of how many) I must say this seems to be the most logical one. Origin relating to the time frame seems practical yet political tide has seemingly taken it too far. The UN declares a level six pandemic in the summer, and I am seeing more license plates labeled DHS government vehicle. One very interesting thing I was discussing with a retired doctor was research on PH levels, Alkalinity, and Cancer that somehow lead to an informative discussion about Colloidal Silver even though it is unrelated. I am no doctor but it has been proven that if used correctly this Colloidal Silver could be used as a measure against such viruses and so far the impact of H1N1 on global population seems to be only 3% making the seasonal flu more deadly. Am I correct in believing that although the topic of H1N1 is extremely interesting because of it's occurrence it may be less of a monster than propaganda and politics make it seem? The question then is, what will prove as the bigger threat? The virus or the governments attempting to contain it? I am interested as to your perspective, please share.

    Yours truly

    polititalk

  25. Hi,

    Whether the Symptons for H1N1 Virus infected will be the same through out the world or it may differ from person to person body conditions? What are the current and latest symptoms regarding it. How to prevent it? What is the method to cure it completely? What are the precautionary methods should be taken for the Childrens and Older people? Please let me know asap.

  26. Profvrr is right the season in these underdeveloped country was so far not congenial for virus now the time has arrived and youn can see the consequences in India and other countries. How this virus is spreading

  27. Profvrr is right the season in these underdeveloped country was so far not congenial for virus now the time has arrived and youn can see the consequences in India and other countries. How this virus is spreading

  28. Ofcourse H1N1 virus is man made. It was released out from the laboratory in 1977. But now it is released once again I think in order to test its efficiency.

  29. Ofcourse H1N1 virus is man made. It was released out from the laboratory in 1977. But now it is released once again I think in order to test its efficiency.

  30. As you probably already know, pig farmers and Jewish and Islamic interest groups have finally convinced the WHO (World Health Organization) to rename the swine flu virus to the influenza H1N1 virus, but what does H1N1 mean?
    Every strain of influenza has an H protein, hemagglutinin, which allows the virus to attach to human host cells, and an N protein, neuraminidase, which destroys mucous. There are multiple types of hemagglutinin and neuraminidase, so the numbers that follow H and N describe the specific type of hemagglutinin and neuraminidase found on that strain. Hemagglutinin and neuraminidase are important because they are essential proteins that allow the virus to infect us. For example, causes a soar throat by clearing the protective layer of mucous usually covering the throat cells with neuraminidase, it then binds to the uncovered cell with hemagglutinin, and finally the virus injects itself into the cell and destroys it.

  31. As you probably already know, pig farmers and Jewish and Islamic interest groups have finally convinced the WHO (World Health Organization) to rename the swine flu virus to the influenza H1N1 virus, but what does H1N1 mean?
    Every strain of influenza has an H protein, hemagglutinin, which allows the virus to attach to human host cells, and an N protein, neuraminidase, which destroys mucous. There are multiple types of hemagglutinin and neuraminidase, so the numbers that follow H and N describe the specific type of hemagglutinin and neuraminidase found on that strain. Hemagglutinin and neuraminidase are important because they are essential proteins that allow the virus to infect us. For example, causes a soar throat by clearing the protective layer of mucous usually covering the throat cells with neuraminidase, it then binds to the uncovered cell with hemagglutinin, and finally the virus injects itself into the cell and destroys it.

  32. his strain of influenza contains viral code fragments from:

    • Human influenza
    • Bird Flu from North America
    • Swine flu from Europe
    • Swine flu from Asia
    so possibility that it is a case of bioterrorism can not be avoided.

  33. impossible to determine the chance ?
    Here is my estimate: 10%. QED.
    Such a chance must be a subjective estimate
    and scientists should not chicken out to give
    subjective estimates, IMO.

  34. impossible to determine the chance ?
    Here is my estimate: 10%. QED.
    Such a chance must be a subjective estimate
    and scientists should not chicken out to give
    subjective estimates, IMO.

  35. you mention Chinese or Russian labs, but isn't it more likely to have
    escaped from an US-lab ?
    China had no advanced flu-labs in 1977, USA was particularly active
    in swineflu research after 1976

  36. you mention Chinese or Russian labs, but isn't it more likely to have
    escaped from an US-lab ?
    China had no advanced flu-labs in 1977, USA was particularly active
    in swineflu research after 1976

  37. Pingback: I guess Big Pharma is driving this report too... - PennJersey.info Forums

  38. 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.

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