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H1N1 influenza adopted novel strategy to move from birds to humans
University of California - Berkeley ^ | Dec 8, 2009 | Unknown

Posted on 12/08/2009 12:58:42 PM PST by decimon

Bird influenza viruses have a variety of strategies to cross the species barrier and spread

The 2009 H1N1 influenza virus used a new strategy to cross from birds into humans, a warning that it has more than one trick up its sleeve to jump the species barrier and become virulent.

In a report in this week's early online edition of the journal Proceedings of the National Academy of Sciences, University of California, Berkeley, researchers show that the H1N1, or swine flu, virus adopted a new mutation in one of its genes distinct from the mutations found in previous flu viruses, including those responsible for the Spanish influenza pandemic of 1918, the "Asian" flu pandemic in 1957 and the "Hong Kong" pandemic of 1968.

Previous influenza strains that crossed from birds into people had a specific point mutation in the bird virus's polymerase gene that allowed the protein to operate efficiently inside humans as well. The polymerase transcribes the virus's RNA, allowing the host to express viral genes, and also copies the viral genome, needed to make new viruses.

The 2009 H1N1 virus retains the bird version of the polymerase, but has a second mutation that seems to suppress the ability of human cells to prevent the bird polymerase from working.

"We were quite shocked when we looked at the swine flu virus, which was clearly replicating in people and other mammalian systems, yet had a polymerase that looked like it was derived from a bird virus, which should not function too well in a human cell type," said UC Berkeley post-doctoral fellow Andrew Mehle of the Department of Molecular and Cell Biology. "The other mutation within the polymerase seems to compensate and allow the enzyme to function."

The researchers also discovered another strategy – one not yet adopted by any known flu virus – by which influenza virus can increase its virulence even more. When a particular human subunit is substituted for one of the three protein subunits that make up the bird polymerase, the new combination makes the polymerase more efficient in human cells.

"This is an extremely rare mutation and a rare combination, which suggests that there may be other ways that haven't emerged yet that these viruses are going to continue to evolve," said Jennifer Doudna, UC Berkeley professor of molecular and cell biology and an investigator in the Howard Hughes Medical Institute.

"As mechanistic biologists, we are hoping that by understanding how the virus works at the molecular level, we will be able to predict with more accuracy how it will evolve."

She suggested that those monitoring influenza outbreaks around the world in search of new variants be on the lookout for this recombination of polymerase subunits, which could herald an uptick in swine flu virulence. The findings also could help scientists develop better antiviral treatments, Mehle and Doudna said.

"The more we can understand the biochemistry and the particular structure of these polymerase complexes, the better we can make rational decisions about drug development," Mehle said.

H1N1, which appeared on the scene earlier this year, was dubbed swine flu because it emerged from pigs, in which human, bird and pig influenza viruses mixed, swapped genes and gave rise to a variant that could infect human cells and reproduce.

While mutations in the surface protein hemagglutinin – indicated by the H in H1N1 – are key to allowing the virus to enter human cells, mutations in the polymerase enzyme are key to the virus's ability to replicate inside human cells. All previous flu strains that entered and were transmitted in humans had a single mutation in the second subunit of the bird polymerase gene, which apparently allowed the enzyme to operate in human cells.

Last year, Mehle and Doudna showed that human cells apparently prevent the three subunits of bird virus polymerases from assembling into a functioning enzyme. A single amino acid switch at position 627 on the second subunit of the polymerase overcomes that inhibition and allows the virus to replicate. Apparently, Mehle said, when the amino acid glutamic acid – typical of most bird virus polymerases – is changed to a lysine, typical of human polymerases, the surface charge of the subunit changes from acidic (negatively charged) to basic (positively charged) and allows assembly of the subunits. Previous studies in mammals have shown that a lysine in that position enhances polymerase activity, increases viral replication and transmission, and in some cases, is associated with increased pathogenicity and death.

In their new study, Mehle and Doudna found that H1N1 has two rare mutations in the second subunit: a serine at position 590 and an arginine at position 591. This combination, which is most common in pigs, apparently has the same effect on surface charge as the mutation at position 627, allowing the polymerase complex to form and function in human cells.

Mehle noted that, in addition to such point mutations, flu viruses also mix and match the three subunits. Both the 1957 and 1968 viruses had polymerases composed of a first subunit from a bird and the other two subunits from humans. H1N1 has a human-like first subunit, while the second and third are bird-like – hence the need for a mutation in the second subunit to make it more human-like.

To see which other combinations might make H1N1 more virulent, they mixed human, avian and pig subunits in culture, replicating the pig "mixing vessel," Mehle said. Several combinations with a human third subunit increased the activity of the polymerase enzyme when other mutations were not present in the second subunit. Viruses with this alteration are now being tested in human cell culture to see if they are more virulent.

"In addition to having individual amino acid changes affecting the ability of the virus to transmit across species and be more pathogenic, we need to think about these entire gene segments being exchanged back and forth," said Doudna, who also is a faculty affiliate of the California Institute for Quantitative Biosciences (QB3). "Those will affect the outcome of disease."

"We are very hopeful that the kind of basic science that we are doing here will have an impact on human health, either at the level of diagnostics or thinking forward to development of antiviral therapeutics," she added.

Mehle and Doudna continue to explore the polymerase to discover what in human cells prevents the assembly of the bird polymerase, and to determine the three-dimensional structure of the enzyme and its three subunits.

###

The work was supported by the National Institute of General Medical Sciences of the National Institutes of Health.


TOPICS: Health/Medicine; Science
KEYWORDS: adopted; birds; creation; evolution; flu; godsgravesglyphs; h1n1; humans; influenza; mexicanflu; move; novel; science; strategy; swineflu; virus

1 posted on 12/08/2009 12:58:43 PM PST by decimon
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To: decimon; DvdMom; neverdem; CholeraJoe; Pharmboy

Swine of a feather ping.


2 posted on 12/08/2009 12:59:42 PM PST by decimon
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To: decimon

thanks, bfl


3 posted on 12/08/2009 1:02:07 PM PST by neverdem (Xin loi minh oi)
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To: decimon; 2ndreconmarine; Fitzcarraldo; Covenantor; Mother Abigail; EBH; Dog Gone; ...

Smokin’ Joe I pinged your list and some other freepers to a new H1N1 thread ping .

thanks :)


4 posted on 12/08/2009 1:12:30 PM PST by DvdMom (Freeper Smokin' Joe does the freeper Avian / H1N1 Ping List)
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To: decimon

Thanks for the H1N1 flu information...


5 posted on 12/08/2009 1:19:01 PM PST by Star Traveler (The God of Abraham, Isaac and Jacob is a Zionist and Jerusalem is the apple of His eye.)
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To: decimon

Yep! Went from birds to the lab to humans. Don’t see that too often...


6 posted on 12/08/2009 1:22:02 PM PST by Hoosier-Daddy ("It does no good to be a super power if you have to worry what the neighbors think." BuffaloJack)
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To: decimon

Evolution in action?


7 posted on 12/08/2009 1:23:50 PM PST by mc6809e
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To: decimon; Pharmboy; Mother Abigail; EBH; vetvetdoug; Smokin' Joe; Global2010; Battle Axe; ...
micro ping

Adaptive strategies of the influenza virus polymerase for replication in humans

That just links the abstract. The pdf is a FReebie.

8 posted on 12/08/2009 1:25:05 PM PST by neverdem (Xin loi minh oi)
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To: decimon

Thanks...very interesting.


9 posted on 12/08/2009 1:29:09 PM PST by Pharmboy (The Stone Age did not end because they ran out of stones...)
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To: Hoosier-Daddy
Went from birds to the lab to humans.

And labs are water dogs, so...

10 posted on 12/08/2009 1:30:33 PM PST by decimon
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To: decimon
H1N1 influenza adopted novel strategy to move from birds to humans

Ya, it's called the help of a labratory ...
11 posted on 12/08/2009 1:46:31 PM PST by Scythian
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To: Scythian
Ya, it's called the help of a labratory ...

That's 'laboratory,' Boris.

Why the conspiracy stuff? Who would do this and to what purpose?

12 posted on 12/08/2009 1:54:25 PM PST by decimon
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To: decimon

She’s a witch!


13 posted on 12/08/2009 2:03:01 PM PST by Hoosier-Daddy ("It does no good to be a super power if you have to worry what the neighbors think." BuffaloJack)
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To: decimon; Scythian
Ask these guys:dead scientists
14 posted on 12/08/2009 2:08:16 PM PST by jonatron
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To: jonatron
Ask these guys:dead scientists

They're dead so I'll ask you. Who would do this and to what purpose?

15 posted on 12/08/2009 2:12:50 PM PST by decimon
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To: Hoosier-Daddy
Yep! Went from birds to the lab to humans. Don’t see that too often...

No kidding.


Frowning takes 68 muscles.
Smiling takes 6.
Pulling this trigger takes 2.
I'm lazy.

16 posted on 12/08/2009 2:12:53 PM PST by The Comedian (Evil can only succeed if good men don't point at it and laugh.)
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To: dangerdoc

bump


17 posted on 12/08/2009 2:13:46 PM PST by dangerdoc
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To: decimon; StayAt HomeMother; Ernest_at_the_Beach; 1ofmanyfree; 21twelve; 24Karet; 2ndDivisionVet; ...

· join list or digest · view topics · view or post blog · bookmark · post a topic · subscribe ·

 
Gods
Graves
Glyphs
Thanks decimon.

To all -- please ping me to other topics which are appropriate for the GGG list.
GGG managers are SunkenCiv, StayAt HomeMother, and Ernest_at_the_Beach
 

·Dogpile · Archaeologica · ArchaeoBlog · Archaeology · Biblical Archaeology Society ·
· Discover · Nat Geographic · Texas AM Anthro News · Yahoo Anthro & Archaeo · Google ·
· The Archaeology Channel · Excerpt, or Link only? · cgk's list of ping lists ·


18 posted on 12/08/2009 4:56:03 PM PST by SunkenCiv (https://secure.freerepublic.com/donate/__Since Jan 3, 2004__Profile updated Monday, January 12, 2009)
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To: decimon

tick, tock, tick, tock...one day one of these things is going to really hit us hard.


19 posted on 12/08/2009 5:04:32 PM PST by americanophile ("For unto you is born this day in the city of David a Savior, who is Christ the Lord.")
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To: Scythian; decimon; SunkenCiv; Beloved Levinite
"This is an extremely rare mutation and a rare combination, which suggests that there may be other ways that haven't emerged yet that these viruses are going to continue to evolve..."

Naturally or with some help and gene splicing from Malthusian vaccine researchers in a lab?


20 posted on 12/08/2009 5:15:50 PM PST by HowlinglyMind-BendingAbsurdity
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To: Pharmboy; neverdem

In picayune mode, I don’t like how they attribute intelligence to a virus. I don’t believe there was any strategy but any number of mutations, one of which allowed it to find new hosts.

I feel better now. Carry on.


21 posted on 12/08/2009 5:21:42 PM PST by decimon
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To: decimon

Sorta like artificial intelligence...


22 posted on 12/08/2009 5:36:48 PM PST by Pharmboy (The Stone Age did not end because they ran out of stones...)
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To: Pharmboy
Sorta like artificial intelligence...

Well, I've been called unreal.

23 posted on 12/08/2009 5:39:48 PM PST by decimon
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To: HowlinglyMind-BendingAbsurdity

Probably the 12 Monkeys was involved.


24 posted on 12/08/2009 7:51:54 PM PST by SunkenCiv (https://secure.freerepublic.com/donate/__Since Jan 3, 2004__Profile updated Monday, January 12, 2009)
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To: SunkenCiv
Closer than you might think:

The Monkeys, the Virus, the Vaccine, and Cancer.

The Virus and the Vaccine: The True Story of a Cancer-Causing Monkey Virus
(in the polio vaccine)

Tetanus Vaccines, Spontaneous Abortions, and Population Control

25 posted on 12/08/2009 8:26:47 PM PST by HowlinglyMind-BendingAbsurdity
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To: decimon

I doubt/hope no one did it deliberately...and I have no idea...who/what/how/when. [I’m just spreading the Paranoia I heard on Coast-to-Coast.]


26 posted on 12/08/2009 9:34:32 PM PST by jonatron
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To: decimon
Some people have looked at the grand battle between parasites and their hosts, and have perceived evidence of intelligent design.
27 posted on 12/09/2009 5:11:27 AM PST by dangerdoc
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To: Hoosier-Daddy

With warehouses of antivirals and vaccines, they had to leave a coupla lab doors open! Those meds expire, can you say pharmaceutical bailout?


28 posted on 12/10/2009 12:22:58 PM PST by momincombatboots (There are times to fight on my knees & times to fight on my feet! I am fully prepared 4 both!)
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To: neverdem
Why do you apologize? for not writing mình xin lỗi? ;-)
29 posted on 12/10/2009 3:59:33 PM PST by AdmSmith
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To: decimon

Not to mention the point mutation in the receptor binding domain change, D225G, that is linked to lung destruction.

But the title is misleading: “H1N1 influenza adopted novel strategy to move from birds to humans” and “Bird influenza viruses have a variety of strategies to cross the species barrier and spread” The virus does not adopt anything and dos not have a strategy. Since the multiplication of the virus is rather sloppy and there are many mutations, with some of them having a higher probability of survival, it gives a genetic drift of the virus. But not according to any plan or design.


30 posted on 12/10/2009 4:10:55 PM PST by AdmSmith
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To: AdmSmith
But the title is misleading: “H1N1 influenza adopted novel strategy to move from birds to humans” and “Bird influenza viruses have a variety of strategies to cross the species barrier and spread” The virus does not adopt anything and dos not have a strategy. Since the multiplication of the virus is rather sloppy and there are many mutations, with some of them having a higher probability of survival, it gives a genetic drift of the virus. But not according to any plan or design.

What I was getting at in post #21. Maybe entirely new microbes come and go without notice for their inability to survive.

31 posted on 12/10/2009 4:22:25 PM PST by decimon
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To: AdmSmith
Why do you apologize? for not writing mình xin lỗi? ;-)

Some veterans recognize my tagline. It seemed appropriate to return to it when Obama beat McCain. I expect nothing good from Obama's Presidency, only overreach. Something good may come from the latter.

32 posted on 12/10/2009 4:31:10 PM PST by neverdem (Xin loi minh oi)
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To: SunkenCiv

http://imva.info/index.php/2009/11/arm-hammer-soda-company/


33 posted on 12/13/2009 4:01:46 PM PST by freedommom
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