Influenza 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
I had no idea scientists were so well versed in OT studies…Good thing I didn't blow off that class at my Jesuit university.
Is it equally plausible that this virus could live in Avian species unimpeded and unchanged, for as long as there was a reservoir? It would seem like if Avian species are the natural host, then there wouldn't quite be a need (or drive) to evolve thus allowing little change from year to year-It seems like the 1918 strain was found in some fowl in Germany a few years back-wouldn't this be along the same line?
I had no idea scientists were so well versed in OT studies…Good thing I didn't blow off that class at my Jesuit university.
Is it equally plausible that this virus could live in Avian species unimpeded and unchanged, for as long as there was a reservoir? It would seem like if Avian species are the natural host, then there wouldn't quite be a need (or drive) to evolve thus allowing little change from year to year-It seems like the 1918 strain was found in some fowl in Germany a few years back-wouldn't this be along the same line?
I very much doubt that the virus could replicate in any species
without significant sequence changes. For example, the genome sequence
encoding the VP1 protein of the poliovirus vaccine strains change 1%
each year as the virus moves through the human population. If the rate
is constant throughout the genome that equates to 75 base changes a
year. For influenza A virus, the rate is in the range of 1.8 x 10–3 to
2.2 x 10–3 nucleotide substitutions/site/year. I doubt there exists a
'neutral' host – but I could be wrong. As for finding the 1918 strain
in fowl….not to my knowledge. That strain has only been
reconstructed from RNA sequences amplified from pathology sections
taken from 1918 influenza victims.
I very much doubt that the virus could replicate in any species
without significant sequence changes. For example, the genome sequence
encoding the VP1 protein of the poliovirus vaccine strains change 1%
each year as the virus moves through the human population. If the rate
is constant throughout the genome that equates to 75 base changes a
year. For influenza A virus, the rate is in the range of 1.8 x 10–3 to
2.2 x 10–3 nucleotide substitutions/site/year. I doubt there exists a
'neutral' host – but I could be wrong. As for finding the 1918 strain
in fowl….not to my knowledge. That strain has only been
reconstructed from RNA sequences amplified from pathology sections
taken from 1918 influenza victims.
If the 1950 H1N1 virus strain was stored in a freezer at that point and then realeased in 1977, wouldn't one would expect it to be nearly identical to the 1950 stain? This theory sounds a bit too cloak and dagger to me.
If the 1950 H1N1 virus strain was stored in a freezer at that point and then realeased in 1977, wouldn't one would expect it to be nearly identical to the 1950 stain? This theory sounds a bit too cloak and dagger to me.
I live in Mexico and we are very confused here about the measures the government is taking against the flu. I have heard that it is not possible in the first 7 days passing the virus person-person, but only in the moment that the symptoms are already visible. Is that true?
I live in Mexico and we are very confused here about the measures the government is taking against the flu. I have heard that it is not possible in the first 7 days passing the virus person-person, but only in the moment that the symptoms are already visible. Is that true?
I remeber about three years ago or so a lab in Cinncianti Ohio sent out about 1500 test kits all over the world to labs for come test for new scientists and ID tests for students. anyway they included by accident the H1N1 virus. because the CDC didn't have it on there deadly pandemic list of virus's. all were recovered but one I had heard. I wonder if that has anything to do with this new outbreak?
I remeber about three years ago or so a lab in Cinncianti Ohio sent out about 1500 test kits all over the world to labs for come test for new scientists and ID tests for students. anyway they included by accident the H1N1 virus. because the CDC didn't have it on there deadly pandemic list of virus's. all were recovered but one I had heard. I wonder if that has anything to do with this new outbreak?
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the united Nations is trying to cut down the world population 93%. With this flu, Flouride in our water, and eating food with almost no nutrients we will Die. This is there goal. World wide Pandemic. everybody in the world wanting a solution. the world Govts. will unify into one New World Order to allegedly solve our problems. as They' ve been doing its all lie. If you think that everything i wrote is Bull Shit. Then you'll just have to see it yourself. the goal is to kill as many as possible by Dec. 31 2012. PLEASE I BEG OF YOU IF YOU DOUBT ME .DO YOUR OWN RESEARCH.
the united Nations is trying to cut down the world population 93%. With this flu, Flouride in our water, and eating food with almost no nutrients we will Die. This is there goal. World wide Pandemic. everybody in the world wanting a solution. the world Govts. will unify into one New World Order to allegedly solve our problems. as They' ve been doing its all lie. If you think that everything i wrote is Bull Shit. Then you'll just have to see it yourself. the goal is to kill as many as possible by Dec. 31 2012. PLEASE I BEG OF YOU IF YOU DOUBT ME .DO YOUR OWN RESEARCH.
This is a new virus that has never been seen before, so it is highly
unlikely. The H1N1 virus included in those kits were the human virus,
which is very different from the swine virus currently circulating.
This is a new virus that has never been seen before, so it is highly
unlikely. The H1N1 virus included in those kits were the human virus,
which is very different from the swine virus currently circulating.
Ryan-
Conspiricy theories are just that…theories. I can accept that nature has it's own way of “Thinning the heard”, but to suggest that the leaders of the world would conspire to “to kill as many as possible by Dec. 31, 2012” is a paranoid delusion. I won't go into biblical references, because their views are just as radical as any conspiricy theorists. I prefer to stick to the empirical facts. The eco-systems around the globe are being upset, and as a result there will certainly be new challenges for all life on the planet. I believe it is a part of the Normal life-cycle of the planet we live on. As it was before, so shall it be again. The only thing that we as humans can count on in this world is change.
Ryan-
Conspiricy theories are just that…theories. I can accept that nature has it's own way of “Thinning the heard”, but to suggest that the leaders of the world would conspire to “to kill as many as possible by Dec. 31, 2012” is a paranoid delusion. I won't go into biblical references, because their views are just as radical as any conspiricy theorists. I prefer to stick to the empirical facts. The eco-systems around the globe are being upset, and as a result there will certainly be new challenges for all life on the planet. I believe it is a part of the Normal life-cycle of the planet we live on. As it was before, so shall it be again. The only thing that we as humans can count on in this world is change.
I read somewhere that this new strain is one that contains parts of the H5N1 virus (bird flu) and other flues, including the H1N1 strain (human), and some genetic material from swine flu, but they're just calling it the H1N1 virus. This is all very confusing, because that would have had to be genetically engineered in a lab and then released into the general public. They (the media) is also saying that it is a rapidly mutating virus (RNA, obviously, because they are unstable). And up in the article it was talking about how the virus in 1970 was very similar to the one in 1950, so it would have to be isolated somewhere and then released. Could this new strain somehow be a similar situation to back then? Could this be genetically engineered? If someone could explain, that would be great.
I read somewhere that this new strain is one that contains parts of the H5N1 virus (bird flu) and other flues, including the H1N1 strain (human), and some genetic material from swine flu, but they're just calling it the H1N1 virus. This is all very confusing, because that would have had to be genetically engineered in a lab and then released into the general public. They (the media) is also saying that it is a rapidly mutating virus (RNA, obviously, because they are unstable). And up in the article it was talking about how the virus in 1970 was very similar to the one in 1950, so it would have to be isolated somewhere and then released. Could this new strain somehow be a similar situation to back then? Could this be genetically engineered? If someone could explain, that would be great.
Thank you Mike. Very well said. 🙂
Thank you Mike. Very well said. 🙂
Mike , you boviously dont understand that Evil exists and is in control. I think you need to do the research and find out what the TRUE empirical facts are. As for the Biblical sequence of events, they are exact and have happened according to the Bible. People research what they want in order to support their own beliefs, not to discover objective truth. All of the brightest minds in the world believe in God as our creator. As they look at the universe there is not explanation to it s greatness and order. For some, they prefer to believe that puncuated Equilibrium is better. They have never studued statistics, if they had they would know that the Bible is TRUE.
There is a reason that evolution is a theory. Do the research and you will find out that Biblical text is fact. It iwill take great great courage to do this is you are an emprical person though. Nothing I can say in detail will convince you. You need to do the research yourself. If you dont then you are resposible for the outcome and your ignorance. To be informed is to know in detail both sides without bias.
Mike , you boviously dont understand that Evil exists and is in control. I think you need to do the research and find out what the TRUE empirical facts are. As for the Biblical sequence of events, they are exact and have happened according to the Bible. People research what they want in order to support their own beliefs, not to discover objective truth. All of the brightest minds in the world believe in God as our creator. As they look at the universe there is not explanation to it s greatness and order. For some, they prefer to believe that puncuated Equilibrium is better. They have never studued statistics, if they had they would know that the Bible is TRUE.
There is a reason that evolution is a theory. Do the research and you will find out that Biblical text is fact. It iwill take great great courage to do this is you are an emprical person though. Nothing I can say in detail will convince you. You need to do the research yourself. If you dont then you are resposible for the outcome and your ignorance. To be informed is to know in detail both sides without bias.
Peak virus shedding occurs about a day before peak symptoms. I would
not say it is impossible to shed virus without symptoms, but in most
cases, shedding is quickly followed by symptoms.
Peak virus shedding occurs about a day before peak symptoms. I would
not say it is impossible to shed virus without symptoms, but in most
cases, shedding is quickly followed by symptoms.
It is nearly identical to the 1950 strain. It would not be identical
because it had already multiplied in humans before the first samples
were taken.
It is nearly identical to the 1950 strain. It would not be identical
because it had already multiplied in humans before the first samples
were taken.
Pigs are infected with many different influenza virus subtypes (H1N1,
H3N2) and viruses with different sets of RNA segments can emerge. It
does not have to be engineered in a lab to have RNAs from so many
different viruses. This is not a virus anyone has seen before, and no
scientist is smart enough to have made it so that it would be
transmitted among humans.
Pigs are infected with many different influenza virus subtypes (H1N1,
H3N2) and viruses with different sets of RNA segments can emerge. It
does not have to be engineered in a lab to have RNAs from so many
different viruses. This is not a virus anyone has seen before, and no
scientist is smart enough to have made it so that it would be
transmitted among humans.
so is this a dna virus or a rna virus which strains does it affect
so is this a dna virus or a rna virus which strains does it affect
I have read the article and all of your replies and want to thank you for a wealth of knowledge and information. I will check back frequently as things progress as you are someone who obviously has the background and access to information and appears to be more than willing to share what you know..
Respectfully,
Stephen
I have read the article and all of your replies and want to thank you for a wealth of knowledge and information. I will check back frequently as things progress as you are someone who obviously has the background and access to information and appears to be more than willing to share what you know..
Respectfully,
Stephen
Dr., I'm a little puzzled by your statement, if I understand it correctly, that no person is intelligent enough to have designed a swine flu virus that can infect humans.
Are you stating that it would be a massively complex undertaking, such as a Manhattan Project, for this to be engineered because of the fantastic complexity at issue?
Thanks,
Matt Dubuque
Dr., I'm a little puzzled by your statement, if I understand it correctly, that no person is intelligent enough to have designed a swine flu virus that can infect humans.
Are you stating that it would require a massively complex undertaking, such as a Manhattan Project, for this to be engineered because of the fantastic complexity at issue?
Thanks,
Matt Dubuque
It's not the complexity of the task that prevents humans from doing
it; it's that we don't know which viral genes, and the sequence of
those genes, to include in the virus so that it will infect humans,
transmit among them, and cause disease. Pigs have millions of
different viruses and one succeeds in infecting humans and passing
among them. How would we know which virus to make among the millions
of possibilities? To make all possible combinations of viruses and
test them all is impossible.
It's not the complexity of the task that prevents humans from doing
it; it's that we don't know which viral genes, and the sequence of
those genes, to include in the virus so that it will infect humans,
transmit among them, and cause disease. Pigs have millions of
different viruses and one succeeds in infecting humans and passing
among them. How would we know which virus to make among the millions
of possibilities? To make all possible combinations of viruses and
test them all is impossible.
Thanks. This is helpful.
So theoretically it would be a far simpler task to engineer or produce a swine flu virus that is more lethal among pigs than to engineer one that could cross the species barrier to humans?
In other words, the reason why one isolate will cross the species barrier and 400 others will fail is still very much a mystery, but tinkering with and engineering a swine flu virus that will remain within pigs is much more straightforward?
My inquiry stems in part because I am persuaded, based on evidence that I regard as competent, that Cuban pig herds were the target of genetically engineered bioattacks. Among other things, my recollection of declassified CIA documents is that, at an absolute minimum, the CIA was actively seeking such a capability.
But your response, as I understand it, is that such an undertaking would be far more straightforward than addressing the fantastic myriad of unanswered questions about crossing the species barrier.
Am I substantially correct in my understanding of your view here?
Thanks for your consummate patience. I do appreciate it. My doctorate is in a very different field!
Matt Dubuque
Thanks. This is helpful.
So theoretically it would be a far simpler task to engineer or produce a swine flu virus that is more lethal among pigs than to engineer one that could cross the species barrier to humans?
In other words, the reason why one isolate will cross the species barrier and 400 others will fail is still very much a mystery, but tinkering with and engineering a swine flu virus that will remain within pigs is much more straightforward?
My inquiry stems in part because I am persuaded, based on evidence that I regard as competent, that Cuban pig herds were the target of genetically engineered bioattacks. Among other things, my recollection of declassified CIA documents is that, at an absolute minimum, the CIA was actively seeking such a capability.
But your response, as I understand it, is that such an undertaking would be far more straightforward than addressing the fantastic myriad of unanswered questions about crossing the species barrier.
Am I substantially correct in my understanding of your view here?
Thanks for your consummate patience. I do appreciate it. My doctorate is in a very different field!
Matt Dubuque
If it was known that humans can be infected with the bird flu and they combined the bird flu with the swine flu so that it purposely infects humans, is it not possible to design this new virus with a little less “complexity”?
If it was known that humans can be infected with the bird flu and they combined the bird flu with the swine flu so that it purposely infects humans, is it not possible to design this new virus with a little less “complexity”?
I am glad that rational thinking still occurs. People need to get beyond the titillating thrill of conspiracy theories and get busy with reality. However, that requires research and work. Thanks for putting facts out there for us to see and understand easily.
I am glad that rational thinking still occurs. People need to get beyond the titillating thrill of conspiracy theories and get busy with reality. However, that requires research and work. Thanks for putting facts out there for us to see and understand easily.
Hello,
could anybody answer this:
how comes that the current year's vaccin is not effectiv on the new “mexico ” H1N1 ?
The H1N1 strain is used in vaccins since 2002 ( probalbly much longer before) ?
thanks
bibi
Hello,
could anybody answer this:
how comes that the current year's vaccin is not effectiv on the new “mexico ” H1N1 ?
The H1N1 strain is used in vaccins since 2002 ( probalbly much longer before) ?
thanks
bibi
Hi Bibi, just an important comment, this new strain is not a “mexico” type. Therefore is more probable that the center of origin was California or Asia and came to Mexico from USA, maybe by a tourist or seasonal worker.
Hi Bibi, just an important comment, this new strain is not a “mexico” type. Therefore is more probable that the center of origin was California or Asia and came to Mexico from USA, maybe by a tourist or seasonal worker.
Maybe I should put it another way (expressed by Dr. Young on TWiV
today, which should go up this weekend). No one could intentionally
make a virulent virus, for any animal, that is completely different or
novel. Perhaps it could be done unintentionally – say an accidental
release from an experimental vaccine lab or other facility. But we
simply don't know how to make a more pathogenic virus. As was pointed
out in TWiV, if someone had made the current H1N1 strain, they would
have at least included resistance to all antivirals.
Maybe I should put it another way (expressed by Dr. Young on TWiV
today, which should go up this weekend). No one could intentionally
make a virulent virus, for any animal, that is completely different or
novel. Perhaps it could be done unintentionally – say an accidental
release from an experimental vaccine lab or other facility. But we
simply don't know how to make a more pathogenic virus. As was pointed
out in TWiV, if someone had made the current H1N1 strain, they would
have at least included resistance to all antivirals.
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.