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Chinese scientists identify deadly gene in H5N1

christian

Valued Member
Chinese scientists identify deadly gene in H5N1
Reuters AlertNet - 06 Nov 2006 09:56:09 GMT

HONG KONG, Nov 6 (Reuters) - Chinese scientists have identified a gene in the H5N1 bird flu virus which they say is responsible for its virulence in poultry, opening the way for new vaccines.

There are many different strains of H5N1, some of which kill more than half the people they infect, while others do little or no harm.

"We can now understand how this virus becomes lethal and the molecular basis for its pathogenicity," Bu Zhigao at the Harbin Veterinary Research Institute told Reuters.

The Chinese researchers zeroed in on the virulent gene after analysing two closely related strains of the H5N1 obtained from infected geese in southern Guangdong province in 1996 -- one highly pathogenic in chickens and the other harmless.

Differences between the two strains were located in four genes, they found.
The scientists designed four genetically modified viruses each containing one of the four genes in question and tested them on laboratory chickens.

Only chickens infected with the modified virus containing the highly pathogenic gene died. The other chickens had no signs of disease, the scientists wrote in the November issue of the Journal of Virology.

"Now that we know the special role of the (highly pathogenic) NS1 gene, we can think about developing a vaccine," Bu said, adding that a vaccine which neutralises the gene known as NS1 could be quickly designed.

"Technically, that can happen very soon, but it is the tests and other procedures that will take a long time."

The scientists are from the Ministry of Agriculture's Animal Influenza Laboratory, the National Key Laboratory of Veterinary Biotechnology, Chinese Academy of Agricultural Sciences, and the Harbin Veterinary Research Institute.

H5N1 remains largely a disease in birds although it has killed over 150 people, mostly in Asia, since 2003. Experts fear that it can spark a pandemic and kill millions of people if it begins to transmit efficiently among humans.
 
Re: Chinese scientists identify deadly gene in H5N1

Which position in NS1 are they referring to? Others have done a similar experiment with pos. 92.

Didn't someone post that poultry VAX target the HA? Since poultry VAX often have a different neuraminidase for tracking which birds were vaccinated, I wonder what the standard poultry VAX NS1 is?

.
 
Re: Chinese scientists identify deadly gene in H5N1

AlaskaDenise said:
Which position in NS1 are they referring to? Others have done a similar experiment with pos. 92.

Didn't someone post that poultry VAX target the HA? Since poultry VAX often have a different neuraminidase for tracking which birds were vaccinated, I wonder what the standard poultry VAX NS1 is?

.

I suspect it is the 5 aa deletion.
 
Re: Chinese scientists identify deadly gene in H5N1

is this the same as stated in May 2004 in:
http://www.pnas.org/cgi/content/full/101/21/8156

H5N1 influenza: A protean pandemic threat
</NOBR><NOBR>Y. Guan<SUP> *,</SUP><SUP> </SUP></NOBR>, <NOBR>L. L. M. Poon<SUP> *</SUP></NOBR>, <NOBR>C. Y. Cheung<SUP> *</SUP></NOBR>, <NOBR>T. M. Ellis<SUP>
Dagger.gif
</SUP></NOBR>, <NOBR>W. Lim<SUP>
sect.gif
</SUP></NOBR>, <NOBR>A. S. Lipatov<SUP> ?</SUP></NOBR>, <NOBR>K. H. Chan<SUP> *</SUP></NOBR>, <NOBR>K. M. Sturm-Ramirez<SUP> ?</SUP></NOBR>, <NOBR>C. L. Cheung<SUP> *</SUP></NOBR>, <NOBR>Y. H. C. Leung<SUP> *</SUP></NOBR>, <NOBR>K. Y. Yuen<SUP> *</SUP></NOBR>, <NOBR>R. G. Webster<SUP> ?</SUP></NOBR>, and <NOBR>J. S. M. Peiris<SUP> *,</SUP></NOBR>
<NOBR><SUP></SUP></NOBR>
<NOBR>
<SUP>..... </SUP>Three genotypes, designated X, Y, and Z, emerged in retail markets
<SUP></SUP>and farms after January 2002 (Table 1 and Fig. 3). These three<SUP> </SUP>genotypes
obtained novel gene constellations by acquiring novel internal protein genes
from avian influenza viruses of unknown<SUP> </SUP>origin (Fig. 1 and data not shown).
All genotype X, Y, and Z<SUP> </SUP>viruses had the 20-aa deletion (positions 49?68)
in the<SUP> </SUP>stalk of the NA that was reported (6) in genotype A viruses<SUP> </SUP>of 2001,
but the genotype B viruses did not. Genotypes B, Y,<SUP> </SUP>and Z viruses, whose
NS gene is derived from a common donor,<SUP> </SUP>shared a 5-aa deletion in the
NS1 protein (positions 80?84)<SUP> </SUP>that was reported previously in H5N1 viruses
isolated in 2001<SUP> </SUP>(6). However, the PB2, PB1, PA, M, and NS genes of
genotype<SUP> </SUP>X viruses differed from those of the H5N1 viruses of 2001,
and<SUP> </SUP>no deletion was observed in the NS gene.<SUP> </SUP>
<SUP></SUP>
<SUP>.....further down....(I can't seem to get it to copy).... at the 3rd to the last paragraph, </SUP>
<SUP>it says once again, that the explanation for virulence is not clear, and is the result of an </SUP>
<SUP>overall constellation of genes rather than just one.</SUP>
<SUP></SUP>
<SUP>.</SUP>

<SUP></SUP>
<SUP></SUP>

<SUP></SUP><!-- null -->

</NOBR>
 
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Re: Chinese scientists identify deadly gene in H5N1

I believe this is reference to the 5 AA deletion that defines the Z genotype. I have to look back at the early sequences froim China. The 20 aa deletion in NA, described in 2004, was actually in many of the 1997 isolates from northern China.
 
Re: Chinese scientists identify deadly gene in H5N1

that report refers to 2001 isolates and says the 5-aa deletion at pos. 80-84 of NS-1 is in the B, Y, & Z genotypes, but genotype X has no such deletion.

As I keep reading that report, it's obvious that it's not a simple situation.

Have more recent isolates changed those earlier conclusions?

.
 
Last edited:
Re: Chinese scientists identify deadly gene in H5N1

I think the earliest isolates with the deletion were from ducks and geese in southern China in 2000. Now, virtually all H5N1's have the deletion.
 
Re: Chinese scientists identify deadly gene in H5N1

It sounds like the latest paper is at position 149, but the tests were on NS1 without the deletion.
 
Re: Chinese scientists identify deadly gene in H5N1

I did a quick read of the paper and didn't see any data on the substitution in the more common deleted gene.
 
Re: Chinese scientists identify deadly gene in H5N1

149 Ala (at position 144 in the deleted gene) is in almost all H5N1's also.
 
Re: Chinese scientists identify deadly gene in H5N1

same story, but some different information...
http://www.newsday.com/news/health/ny-hsflu074964666nov07,0,1409518.story?coll=ny-health-print

Hope in bird flu finding

Vaccine experts hail discovery of gene that causes virus to spread in some chicken flocks while bypassing others

BY DELTHIA RICKS
Newsday Staff Writer

November 7, 2006


Scientists in China have pinpointed the virulence gene in chickens infected with the avian influenza virus, an advance that adds to the understanding of an ever-changing microbe and spotlights a new target for vaccines.

The discovery is being hailed by vaccine experts as well as global public health officials who say the finding helps explain why infection with the H5N1 virus often sweeps mercilessly through flocks. With the killer gene in hand, scientists say they now can begin to unlock a host of viral secrets, shedding light on why in some instances H5N1 kills explosively while in others instances infected birds escape unscathed.

A similar pattern also has been seen in human infections with H5N1: swift death or people walking away unharmed from bird flu.

Reporting in the current issue of the Journal of Virology, Dr. Bu Zhigao and his team elucidated features of the bird flu gene, one that at least one U.S. expert is calling the ballistic missile inside H5N1. The gene, which is dubbed NS1, has been suspected for a while as having devastating consequences. Now that it has been isolated, scientists can determine what makes it tick.

"We have suspected in H5N1 infections involving humans that NS1 is probably one component that makes the disease so virulent. It probably blocks our body's interferon," one of the immune system's proteins that fight viral infections, said Dr. Michael Greger, director of public health and animal agriculture at the Humane Society of the United States.

Dr. Pascal James Imperato, chairman of the department of preventive medicine at SUNY Downstate Medical Center in Brooklyn, said avian influenza experts have long been aware of distinct bird flu strains: high pathogenicity and low pathogenicity, references that indicate a strain's capacity to confer disease. Scientists in China have now laid the groundwork to dissect the gene that lies at the heart of a global pandemic among birds.

"They found through fairly elaborate molecular biological experimentation that the NS1 gene is fairly critical in the severity of the disease. So this means this particular gene plays a very significant role. With the absence of the gene the disease is not as virulent," Imperato said.

Dr. John Treanor, a vaccine expert at the University of Rochester, said there may be other genes like NS1 that have yet to be found (we could offeer some suggestions!). "There has been an interest in understanding why some cases in humans have been so severe. Getting clues like this may help out with that," he said.

Greger said lethal strains of H5N1 tend to spread so fast among chickens because thousands are too often kept in close quarters, a situation that not only aids transmission but provides ample opportunity for the virus to mutate.

"This outbreak often has been blamed on backyard birds," said Greger, author of the book "Bird Flu: A Virus of Our Own Hatching."

"But what has happened in recent years is an intensification of the Tyson-model of industrial poultry production in southern China. In those kinds of conditions birds are beak-to-beak. Mutations can occur quickly. These chicken factories are nothing more than pandemic roulette."

.
 
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