Genes found in nature yield 1918-like virus with pandemic potential

[Shiloh]

Source: http://www.news.wisc.edu/22918

Genes found in nature yield 1918-like virus with pandemic potential
June 11, 2014
by Terry Devitt

An international team of researchers has shown that circulating avian influenza viruses contain all the genetic ingredients necessary to underpin the emergence of a virus similar to the deadly 1918 influenza virus.

Searching public databases, the researchers, led by Yoshihiro Kawaoka of the University of Wisconsin-Madison, identified eight genes from influenza viruses isolated from wild ducks that possessed remarkable genetic similarities to the genes that made up the 1918 pandemic flu virus. The 1918 or ?Spanish flu? pandemic was one of recorded history?s most devastating outbreaks of disease, resulting in an estimated 40 million deaths worldwide.

The new work was published today (June 11, 2014) in the journal Cell Host & Microbe. It shows that ?there are gene pools in nature that have the potential to cause a severe pandemic in the future,? says Kawaoka, an international authority on influenza and the senior author of the new report...

[tetano]

Re: Genes found in nature yield 1918-like virus with pandemic potential

American scientists controversially recreate deadly Spanish Flu virus



The extinct influenza virus that caused the worst flu pandemic in history has been recreated from fragments of avian flu found in wild ducks in a controversial experiment to show how easy it would be for the deadly flu strain to reemerge today.

Scientists said the study involved infecting laboratory ferrets with close copies of the 1918 virus ? which was responsible for the Spanish Flu pandemic that killed an estimated 50 million people ? to see how easy it can be transmitted in the best animal model of the human disease.

But other researchers have denounced the research as foolhardy and dangerous. Critics said that any benefits of the attempts to recreate 1918-like flu viruses from existing avian flu strains do not justify the catastrophic risks if such a genetically engineered virus were to escape either deliberately or accidentally from the laboratory and cause a deadly influenza pandemic.

...

http://www.independent.co.uk/news/science/american-scientists-controversially-recreate-deadly-spanish-flu-virus-9529707.html

[tetano]

Re: Genes found in nature yield 1918-like virus with pandemic potential

The original article

[gsgs]

Re: Genes found in nature yield 1918-like virus with pandemic potential

Found it here:

http://www.cell.com/cell-host-microbe/abstract/S1931-3128%2814%2900163-2

7 amino acid in polymerases and HA conferred
droplet transmission in ferrets,

Interestingly, for most viral proteins
(except for hemagglutinin [HA], neuraminidase [NA], and PB1-
F2), we found avian influenza virus proteins that differed from
their 1918 counterparts by only a limited number of amino acids
(Table S1).

[that's because of the bird-index (they didn't know that ?!) 1918 flu has
46=8+7+10+9+7+5 amino-acid differences from the index in the 6 inner segments.]


PB2 of A/blue-winged teal/Ohio/926/2002 (H3N8),
PB1 of A/blue-winged teal/Alberta(ALB)/286/77(H3N6),
PA of A/pintail duck/ALB/219/77 (H1N1),
HA of A/pintail duck/ALB/238/79 (H1N1),
NP of A/blue-winged teal/Ohio/908/2002 (H1N1),
NA of A/mallard/duck/ALB/46/77 (H1N1),
M of A/duck/Germany/113/95(H9N2),
NS of A/canvasback duck/Alberta/102/76 (H3N6),

-------------------
-
N375S,E383D,R584H
R269K,S400L,K716R,

V105M,L136M

T121A
D209N,R224G,S291N
-------------------------


8 , 6, 9 , 7 , 6, 4 amino acids from the 1918 virus.

[so it has already 0+1+1+2+1+1=6 of the 46 mutations from 1918 in the inner segments (13%),
which presumably almost randomly appeared in some birds, but not systematically, not together,
I wished they had taken the pure bird-index-virus plus HA,NA]

[I remember, Taubenberger et.al. did something similar some years ago,
they called the bird-index "avian consensus", was it mentioned ? The word
"consensus" doesn't appear in the Kawaoka paper (57 pages .pdf, 14+suppl.)]

================================================== =====

the Taubenberger paper : (2012)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3416129/

http://www.flutrackers.com/forum/showpost.php?p=489304

> segments 1,2,3,5,6,7,8, from A/Green Wing Teal/Ohio/175/1986 (H2N1)
> segment 4 from A/mallard/Ohio/265/1987 (H1N9)
> similar to the avian influenza virus consensus (see below),


3,0,7,-,3,-,0,1 A/Green Wing Teal/Ohio/175/1986 (H2N1) [9004]
4,3,5,-,2,-,0,1 A/mallard/Ohio/265/1987 (H1N9) [10751]
8,7,10,-,9,-,7,5 A/Brevig Mission/1/1918(H1N1) [3]
0,0,0,0,0,0,0,0 A/bird-index-a/2000(H3N8) {1]


==============================================


A/blue-winged teal/Ohio/926/2002 (H3N8)
A/blue-winged teal/Alberta(ALB)/286/77(H3N6)
A/pintail duck/ALB/219/77 (H1N1)
====
A/blue-winged teal/Ohio/908/2002 (H1N1)
====
A/duck/Germany/113/95(H9N2)
A/canvasback duck/Alberta/102/76 (H3N6)

A/pintail duck/ALB/238/79 (H1N1)
A/mallard/duck/ALB/46/77 (H1N1)
8,6,9,33,7,31,6,4
20 (PB1-F2),

0,1,4,3,3,1
2,3,-,-,1,-
5,0,3,2,0,5
3,1,6,3,0,2
3,4,8,2,2,2
5,2,1,2,1,0
2,1,3,5,1,3
4,3,-,-,1,3

-------------------reading the whole paper ...-----------------------
Interestingly, for most viral proteins
(except for hemagglutinin [HA], neuraminidase [NA], and PB1-
F2), we found avian influenza virus proteins that differed from
their 1918 counterparts by only a limited number of amino acids
(Table S1).

grew well in Madin-Darby canine kidney (MDCK) cells and
embryonated chicken eggs
growth was comparable to that of the 1918 virus

intermediate pathogenicity in mice, mild in ferrets

The 1918 PB2 and HA Genes Contribute to Enhanced
Pathogenicity and Transmissibility in Ferrets

We were unable to generate 1918-like avian
PB2-627K:HA-190D/225D virus in embryonated chicken eggs,

PB2-627K:HA-89ED/190D/225D virus group and found three
additional mutations, HA-S113N, PB2-A684D, and PA-V253M


(E627K and A684D in PB2;
E89D, S113N, I187T, E190D, G225D, and D265V in HA; V253M
in PA; and T232I in NP) may be associated with efficient 1918-
like avian virus transmission in ferrets.


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