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Tracking the next pandemic: Avian Flu Talk

Altered Receptor Binding in H5N1 Bird Flu in Indo

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Jhetta View Drop Down
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Evolution and adaptation of H5N1 influenza virus in avian and human hosts in Indonesia and Vietnam.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16713612&query_hl=1&itool=pubmed_docsum

Smith GJ, Naipospos TS, Nguyen TD, de Jong MD, Vijaykrishna D, Usman TB, Hassan SS, Nguyen TV, Dao TV, Bui NA, Leung YH, Cheung CL, Rayner JM, Zhang JX, Zhang LJ, Poon LL, Li KS, Nguyen VC, Hien TT, Farrar J, Webster RG, Chen H, Peiris JS, Guan Y.

State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China; Joint Influenza Research Center (SUMC and HKU), Shantou University Medical College, Shantou, Guangdong 515031, China.

Highly pathogenic avian influenza virus H5N1 is endemic in poultry in East and Southeast Asia with disease outbreaks recently spreading to parts of central Asia, Europe and Africa. Continued interspecies transmission to humans has been reported in Vietnam, Thailand, Cambodia, Indonesia and China, causing pandemic concern. Here, we genetically characterize 82 H5N1 viruses isolated from poultry throughout Indonesia and Vietnam and 11 human isolates from southern Vietnam together with sequence data available in public databases to address questions relevant to virus introduction, endemicity and evolution.
 
Phylogenetic analysis shows that all viruses from Indonesia form a distinct sublineage of H5N1 genotype Z viruses suggesting this outbreak likely originated from a single introduction that spread throughout the country during the past two years.
 
Continued virus activities in Indonesia were attributed to transmission via poultry movement within the country rather than through repeated introductions by bird migration. Within Indonesia and Vietnam, H5N1 viruses have evolved over time into geographically distinct groups within each country. Molecular analysis of the H5N1 genotype Z genome shows that only the M2 and PB1-F2 genes were under positive selection, suggesting that these genes might be involved in adaptation of this virus to new hosts following interspecies transmission. At the amino acid level 12 residues were under positive selection in those genotype Z viruses, in the HA and PB1-F2 proteins. Some of these residues were more frequently observed in human isolates than in avian isolates and are related to viral antigenicity and receptor binding. Our study provides insight into the ongoing evolution of H5N1 influenza viruses that are transmitting in diverse avian species and at the interface between avian and human hosts.

PMID: 16713612 [PubMed - as supplied by publisher]
 
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jhetta hi im kinda new here are ya stll on line i have a question
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J Virol. 2005 Sep;79(18):11788-800. Related Articles, < =1.2> < =1.2> Links
Click here to read Click here to read 
Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16140756&query_hl=4&itool=pubmed_docsum


Maines TR, Lu XH, Erb SM, Edwards L, Guarner J, Greer PW, Nguyen DC, Szretter KJ, Chen LM, Thawatsupha P, Chittaganpitch M, Waicharoen S, Nguyen DT, Nguyen T, Nguyen HH, Kim JH, Hoang LT, Kang C, Phuong LS, Lim W, Zaki S, Donis RO, Cox NJ, Katz JM, Tumpey TM.

Influenza Branch, Mail Stop G-16, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, N.E., Atlanta, GA 30333, USA.

The spread of highly pathogenic avian influenza H5N1 viruses across Asia in 2003 and 2004 devastated domestic poultry populations and resulted in the largest and most lethal H5N1 virus outbreak in humans to date. To better understand the potential of H5N1 viruses isolated during this epizootic event to cause disease in mammals, we used the mouse and ferret models to evaluate the relative virulence of selected 2003 and 2004 H5N1 viruses representing multiple genetic and geographical groups and compared them to earlier H5N1 strains isolated from humans.

Four of five human isolates tested were highly lethal for both mice and ferrets and exhibited a substantially greater level of virulence in ferrets than other H5N1 viruses isolated from humans since 1997.

One human isolate and all four avian isolates tested were found to be of low virulence in either animal. The highly virulent viruses replicated to high titers in the mouse and ferret respiratory tracts and spread to multiple organs, including the brain.
 
Rapid disease progression and high lethality rates in ferrets distinguished the highly virulent 2004 H5N1 viruses from the 1997 H5N1 viruses.
 
A pair of viruses isolated from the same patient differed by eight amino acids, including a Lys/Glu disparity at 627 of PB2, previously identified as an H5N1 virulence factor in mice.
 
The virus possessing Glu at 627 of PB2 exhibited only a modest decrease in virulence in mice and was highly virulent in ferrets, indicating that for this virus pair, the K627E PB2 difference did not have a prevailing effect on virulence in mice or ferrets.
 
Our results demonstrate the general equivalence of mouse and ferret models for assessment of the virulence of 2003 and 2004 H5N1 viruses. However, the apparent enhancement of virulence of these viruses in humans in 2004 was better reflected in the ferret.
 
 
Journal of Virology, February 2005, p. 2191-2198, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2191-2198.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Lethality to Ferrets of H5N1 Influenza Viruses Isolated from Humans and Poultry in 2004

Elena A. Govorkova,1 Jerold E. Rehg,2 Scott Krauss,1 Hui-Ling Yen,1 Yi Guan,3 Malik Peiris,3 Tien D. Nguyen,4 Thi H. Hanh,5 Pilipan Puthavathana,6 Hoang T. Long,5 Chantanee Buranathai,7 Wilina Lim,8 Robert G. Webster,1,9* and Erich Hoffmann1

Departments of Infectious Diseases,1 Pathology, St. Jude Children's Research Hospital,2 Department of Pathology, University of Tennessee, Memphis, Tennessee,9 Joint Influenza Research Center (Shantou University Medical College and Hong Kong University), Shantou University Medical College, Shantou, Guangdong,3 Government Virus Unit, Department of Health, Hong Kong, Special Administrative Region, People's Republic of China,8 Department of Virology, National Institute of Veterinary Research, Ministry of Agriculture and Rural Development,4 Virology Department, National Institute of Hygiene and Epidemiology, Hanoi, Vietnam,5 Department of Microbiology, Sriraj Hospital,6 Department of Livestock Development, National Institute of Animal Health, Bangkok, Thailand7

Received 15 July 2004/ Accepted 23 September 2004

The 2004 outbreaks of H5N1 influenza viruses in Vietnam and Thailand were highly lethal to humans and to poultry; therefore, newly emerging avian influenza A viruses pose a continued threat, not only to avian species but also to humans. We studied the pathogenicity of four human and nine avian H5N1/04 influenza viruses in ferrets (an excellent model for influenza studies). All four human isolates were fatal to intranasally inoculated ferrets.


The human isolate A/Vietnam/1203/04 (H5N1) was the most pathogenic isolate; the severity of disease was associated with a broad tissue tropism and high virus titers in multiple organs, including the brain. High fever, weight loss, anorexia, extreme lethargy, and diarrhea were observed. Two avian H5N1/04 isolates were as pathogenic as the human viruses, causing lethal systemic infections in ferrets. Seven of nine H5N1/04 viruses isolated from avian species caused mild infections, with virus replication restricted to the upper respiratory tract. All chicken isolates were nonlethal to ferrets. A sequence analysis revealed polybasic amino acids in the hemagglutinin connecting peptides of all H5N1/04 viruses, indicating that multiple molecular differences in other genes are important for a high level of virulence. Interestingly, the human A/Vietnam/1203/04 isolate had a lysine substitution at position 627 of PB2 and had one to eight amino acid changes in all gene products except that of the M1 gene, unlike the A/chicken/Vietnam/C58/04 and A/quail/Vietnam/36/04 viruses.

Our results indicate that viruses that are lethal to mammals are circulating among birds in Asia and suggest that pathogenicity in ferrets, and perhaps humans, reflects a complex combination of different residues rather than a single amino acid difference.


* Corresponding author. Mailing address: Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794. Phone: (901) 495-3400. Fax: (901) 523-2622. E-mail: robert.webster@stjude.org
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Jhetta View Drop Down
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Jhetta Quote  Post ReplyReply Direct Link To This Post Posted: June 09 2006 at 8:47pm

Sherie,

The site reports Animals infected with H5N1... it reports how many were infected, how many died, where they were located, etc.
 
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i dont know how to copy stuff but have ya been to the oie website they have some pretty good news on avian flu in birds
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it list each country with dates and how many animals killes and labs where it was tested and stuff i dont understand
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whats a link
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the web thing is oie.int
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did i do that or you but yes thats it
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 09 2006 at 9:10pm
ok thanks
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JHETTA----- Here's more on the ferrets, mice and vaccine development. I've read about this before, thought it made perfect scientific sense and St. Jude's is nothing if not reputable. This seems to be updated info and GOOD news. Please see if you can find more, I'll do the same. (As others, reading for months but first post... California here too)

 

Special report:Global fight against bird flu

    LOS ANGELES, May 2 (Xinhua) -- A commercially developed vaccine has successfully protected mice and ferrets against the highly pathogenic H5N1 avian influenza virus, U.S. scientists reported on Tuesday.

    The vaccine, developed by Vical Incorporated in San Diego, California, is also effective against multiple human and bird influenza strains, according to researchers at the St. Jude Children's Research Hospital in Memphis, Tennessee, where the animal test was conducted.

    This finding suggests that such a vaccine would protect humans against multiple variants of the bird and human influenza viruses, said Richard Webby, the doctor who led the study.

    Such a vaccine could protect humans against an H5N1 "bird flu" virus that mutates so that it adapts to humans and can readily spread from person to person, Webby said. Flu experts and public health officials fear that such an H5N1 variant would trigger a worldwide human flu epidemic.

    In the study, the investigators used two versions of Vical's DNA-based vaccine. One vaccine was directed against three viral proteins: the nucleoprotein (NP), the matrix protein (M2) and hemagglutinin (H5). The other version of the vaccine contained only the NP and the M2.

    The NP and the M2 proteins are "conserved" proteins that generally do not mutate quickly, and therefore are slow to avoid immune responses triggered by the vaccine.

    The H5 is a highly variable protein on the surface of the flu virus that is critical to their ability to infect cells. This variable protein is known to mutate readily, thereby foiling previous immune responses it triggered -- whether due to natural exposure or vaccination.

    The study included 16 mice or six ferrets in each vaccine or control group. According to Webby, the full, three-component vaccine provided complete protection in mice against lethal challenges with a highly virulent H5N1 virus strain (Vietnam/1203/2004).

    The second vaccine also provided significant protection against several strains of human influenza virus as well as the H5N1 "birdflu" strain, said the researchers. Fourteen of the 16 mice in each of two vaccine groups survived with moderate weight loss.

    "Such cross-protection against bird and human influenza is considered by researchers to be the 'Holy Grail' of flu vaccines, "Webby said in a statement.

    "By stimulating immune responses against targets not likely to mutate, the vaccine could trigger an immune defense against a broad range of variants of the virus."

    If a pandemic flu strain is emerging, this approach may provide broad-based protection prior to the identification and development of a precisely matched hemagglutinin vaccine component, noted the researchers.

    "Even if the bird flu virus mutates so it becomes adapted to humans, this kind of cross protection will allow the immune system to track and attack such an emerging new variant without missing a beat," Webby said.

    "We wouldn't have to wait to start developing a vaccine against it until after the original virus mutated."

    "We are encouraged by the protection afforded by our avian flu vaccine and by the cross-protection data," said Vijay B. Samant, president and chief executive officer of Vical, adding the company is "advancing toward human trial of the flu vaccine." Enditem

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 10 2006 at 12:50am
now all they need do is make 6 billion doses
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Welcome Christy, we are happy you've decided to join in.

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< = defer>winDirVariable="C:/WINNT" Thanks Annie, and you're right Kilt, I'm not counting on vaccines being available to the general public any time soon, but it's a start. Human trials are underway and since it's not mutation specific, at least production can begin without having to design it for a specific bug.  Pandemic aside, its ability to recoginize new mutations is a vast improvement in flu vaccines.  I found a bit more at St. Judes site if anyone is interested. Only posted it as more on the ferret/mice posts.
 
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 10 2006 at 5:32am
Welcome Christy...
 
Glad your joined us...Feel free to post any questions.
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Originally posted by JoeNeubarth JoeNeubarth wrote:

Originally posted by pheasant pheasant wrote:

i wasn't joking.................has the virus mutated...yes or no ?


The answer is YES!

What they uncovered is the fact that some of the viral samples have made the change necessary for Ease of Transmission. 

What we don't know is how wide spread this mutation is.  Was it just limited to that part of Indonesia or is it more widely entrenched?  We will know in the next few weeks and months.

What I do know is that IT IS COMING.  When the sneezing starts, it will travel the oceans in pressurized aluminum cylinders and make itself known the world over.  November.


This is not good Joe. There are a number of us here to look at this particular thread, the specific gene data, and recognize the jump has occured. It is like putting a sneezing child in a preschool and wondering if the other kids will get it.

Since I don't have a lot of positive things to say here, I do think some the virologists I have talked to should be in labs trying to adapt a new vaccine based on this data.

We need some multiple researcher backup here. Most of all we need a government health person to take this on full in the face, and comment.
Do we have that?
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 10 2006 at 9:15am

MedClinician, I think we do have but, the Indonesian government hinders investigations and research inside Indonesia. Do you read the posts on fluwiki? Last night Dr Jeremijenko made some comments that were very worrisome about the political hinderances in Indonesia concerning bf. The situation is deplorable.

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I've been thinking for about a month now that countries need to get together on prohibiting travel and trade if the Indonesia government doesn't get their act together.  Infact, if they wait any longer, they may have no choice.  This is good news on a vaccine.  I say let's take a good chunk of what we normally give to the WHO and pay some of the best scientists to do their own research.  There's too much at stake to play administrative footsie - and we're running out of time, time which would be better spent getting a vaccine upfront.

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My question is the vaccine that they are now working on, will it stop the cytokine storm by allowing the body to recognize many varients,  and only focus on those cells and help prevent ARDS? This is pretty technical stuff and I don't want to think I understand, but really don't. Thanks, Jo
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We have to remember that the report of success is based on animal models that do not necessarily transfer to humans.  While this information is encouraging.... we have to remember there are many many variables that could preclude success. 
 
We also have to remember that most of these companies are publicly traded and that they use press releases to help inflate the price of their stock.  Though it is noted that the researcher themselves do not own stock it is likelythe research was funded by Vical.
 
Evolutionary characterization of the six internal genes of H5N1 human influenza A virus
 
 
 
The success of a commercially produced vaccine in protecting laboratory animals from bird flu virus during studies performed at St. Jude suggests that it would protect humans if the virus mutates and acquires the ability to spread from person to person

Researchers at St. Jude Children’s Research Hospital said they have taken a significant step in the development of a vaccine that could protect humans against a bird flu virus if it mutates into a form that can be passed from person to person.

The investigators announced they had protected mice and ferrets against a highly lethal avian influenza virus using a commercially developed DNA-based vaccine that was previously shown to protect animals against multiple human flu strains.
 
The vaccine’s ability to protect against both human flu viruses and H5N1—the bird flu virus (Jhetta in animals)—suggests that such a vaccine could protect humans if an H5N1 virus mutates so that it can pass easily from person to person, according to Richard Webby, PhD, assistant member of Infectious Diseases at St. Jude.

These findings are important because international research and public health officials fear that if H5N1 adapts to humans and permits person-to-person transmission, a resulting pandemic (worldwide epidemic) could kill many tens of millions of people and cause severe economic damage to countries.

The vaccine was developed by Vical Inc. of San Diego, California, using their patented technology. Webby presented the findings of this study at the U.S. Public Health Service Professional Conference in Denver, Colorado, May 3.

“Our expertise in this area of H5N1 vaccine research is what prompted Vical to invite us to join them in this important work,” Webby said. Webby is the subcontractor for Vical on a grant from the National Institute of Allergies and Infectious Diseases to study this vaccine.
 
If H5N1 mutates and becomes fully adapted to humans, health officials will benefit by having access to a number of different options for vaccines and antiviral agents, according to Webby. “This DNA-based vaccine overcomes some technical problems that slow production of conventional vaccines and reduces their ability to protect against viruses that mutate,” Webby said. 

The investigators used two versions of Vical’s multi-component, DNA-based vaccine in the studies. One vaccine was directed against three viral proteins: NP and M2, which are “conserved” proteins that generally do not mutate quickly and therefore are slow to avoid immune responses triggered by the vaccine; and H5, a “variable” protein on the surface of the bird and human flu viruses that is critical to their ability to infect cells. This variable protein is known to mutate readily, thereby foiling previous immune responses it triggered—whether due to natural exposure or vaccination. The other version of the vaccine contained only the two conserved viral proteins.

In the St. Jude study, the full, three-component vaccine (H5, NP and M2) provided complete protection in mice against lethal challenges with a highly virulent (Vietnam/1203/2004) H5N1 avian influenza virus. Moreover, previous studies showed that a smaller version of the vaccine containing only the NP and M2 components provided significant protection against several strains of human influenza virus as well as the H5N1 “bird flu” strain.

“Such cross-protection against bird and human influenza is considered by researchers to be the ‘Holy Grail’ of flu vaccines,” noted Webby. “By stimulating immune responses against targets not likely to mutate, the vaccine could trigger an immune defense against a broad range of variants of the virus.”

“Even if the bird flu virus mutates so it becomes adapted to humans, this kind of cross protection will allow the immune system to track and attack such an emerging new variant without missing a beat,” Webby said. “We wouldn’t have to wait to start developing a vaccine against it until after the original virus mutated.”

Vical made the vaccine by inserting the gene for each protein into a separate plasmid—a small circular piece of DNA normally found in bacteria. Each plasmid was inserted into different bacteria (Escherichia coli) and the bacteria grown into large numbers in a fermentation vat. As the bacteria multiplied they copied the plasmids containing each gene. The genes were then extracted and combined in a solution with another ingredient designed to increase the ability of the vaccine to stimulate the immune system.

Neither Webby nor the other members of the St. Jude team own stock in Vical or have any financial interest in this project. 

If you would like to comment on this article, click here

Last update: May 2006

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Originally posted by rodin33 rodin33 wrote:

 Last night Dr Jeremijenko made some comments that were very worrisome about the political hinderances in Indonesia concerning bf. The situation is deplorable.
Rodin33, I would love to read that post. If you come across it could you post it in a new thread in the discussion forum maybe under the topic Dr. Jeremijenko comments. Thanks. Annie
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well if they develop a vacine with the current strand and vac all people and livestock wouldnt that stop or really slow the spread and mutation of the virus?
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ops144, once the pandemic strain emerges, it will take at the very least six months to make enough vaccine to vaccinate some of the essential front lines ie doctors, nurses, emergency personell etc. If Dr Niman's Recombonics approach to predicting that strain works (and we won't know that unless he gets the sequences released) then perhaps a vaccine could be made ahead of time, unfortunatly it doesn't look like that is going to happen in time.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 10 2006 at 1:59pm
i under stand that but why not make a vac for the strand now thats infecting people and animals?
 
if they stop it before it has a chance to keep infecting people with the possibility to mutate to h2h that might win the fight right..
 
if the strand or strands out there now are stopped before the change
that will also win the battle am i right or am i missing something?
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 10 2006 at 2:18pm
ops144,  a vaccine made from any of those strands would offer very little if any protection from the emergant strain. The best chance we have is to stop it and or contain it in the country it emerges in. But there is very little chance that will happen
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Jhetta Quote  Post ReplyReply Direct Link To This Post Posted: June 10 2006 at 2:19pm
Originally posted by ops144 ops144 wrote:

i under stand that but why not make a vac for the strand now thats infecting people and animals?
 
if they stop it before it has a chance to keep infecting people with the possibility to mutate to h2h that might win the fight right..
 
if the strand or strands out there now are stopped before the change
that will also win the battle am i right or am i missing something?
 
We do not know how many strians there are.  And it takes time to develop the vaccine and then more time to get it into poduction.  For new technology it is likley they would have to build a new plant to produce it and this takes time.
 
This info comes from a study that used only Six human H5N1 viruses. The samples were collected and isolated within a single year in the same geographical location and the 6 H5N1 samples had high nucleotide and amino acid variation among the internal genes
 
They found at least two antigenic groups. And variation among the 6 human H5N1 viruses could be observed in all eight RNA segments. While amino acid differences occurred not only in the surface HA protein, but also in the internal proteins of these viruses.
 
A number of amino acid changes were observed in all internal proteins. Both human and poultry H5N1 viruses possessed human-like amino acids in the NP, PB2 and M2 proteins that correlated with host-determinant factors.

Evolutionary characterization of the six internal genes of H5N1 human influenza A virus
 
http://vir.sgmjournals.org/cgi/content/full/81/5/1293

" Thus, genetic analysis of H5N1 viruses isolated from birds and humans in Hong Kong suggests that these viruses are inherently highly variable and prone to rapid change. "....
 
"Human H5N1 influenza A viruses are separated into two antigenic groups on the basis of haemagglutination-inhibition tests (Bender et al., 1999 ; Shortridge et al., 1998 ). In agreement with the above reports, we also confirmed the presence of two antigenic groups among human H5N1 influenza A viruses on the basis of haemagglutination-inhibition tests with mouse immune sera as well as plaque-neutralization tests with post-infection ferret anti-sera (data not shown). Evolutionary analysis further indicated that the HA and NA genes are divided into two minor evolutionary clades (Bender et al., 1999 ; Suarez et al., 1998 ). Through a series of evolutionary analyses, the six internal genes of human H5N1 viruses were also found to have diverged generally into two distinguishable evolutionary groups. All RNA segments were, therefore, confirmed to have divided into essentially two minor evolutionary lineages, including HK156-like (i) and HK483- or HK482-like (ii) strains. However, the phylogenetic locations of the PB2, NP and NS genes of HK481 were somewhat divergent from those of the above two groups. It has been reported before that phylogenetic analysis of the internal genes of H5N1 viruses isolated from poultry in Hong Kong also revealed divergence into two minor evolutionary lineages (Zhou et al., 1999 ). Thus, genetic analysis of H5N1 viruses isolated from birds and humans in Hong Kong suggests that these viruses are inherently highly variable and prone to rapid change.

Coupled with previous evidence (Bender et al., 1999 ; Suarez et al., 1998 ), it is apparent that variation among human H5N1 viruses could be observed in all eight RNA segments and that subsequent amino acid differences occurred not only in the surface HA protein, but also in the internal proteins of these viruses. In fact, a number of amino acid changes were observed in all internal proteins of Hong Kong poultry H5N1 viruses (Zhou et al., 1999 ). Moreover, human and poultry H5N1 viruses (Zhou et al., 1999 ) possessed human-like amino acids in the NP, PB2 and M2 proteins that correlated with host-determinant factors. Considering the short time span within which human H5N1 viruses were isolated in a local region, it was particularly intriguing that the high nucleotide and amino acid variation among the internal genes of H5N1 viruses was actually more pronounced than that observed among epidemic human H3N2 influenza viruses isolated in different years (Lindstrom et al., 1998 ).....

However, despite the highly variable nature of H5N1 viruses, both genetically and antigenically, the results of vaccination experiments in mice have suggested that there is a relatively high degree of cross-protective immunity elicited by human H5N1 viruses"
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We can't stop it, it's everywhere, changing all the time.  There is not enough vaccine that fits it, to be able to stop it.  We can't change the animal husbandry practices or the dire conditions of poverty or the human
populations encroaching on the wild herds or the wild birds that carry it to domestic poultry....fast enough to stop it.
 
 
We need to be more advanced in our science as explained below
in order to stop paramyxoviruses.
 
 

Pathogenic paramyxoviruses

A number of important human diseases are caused by paramyxoviruses. These include mumps, measles, which caused 745,000 deaths in 2001 and respiratory syncytial virus (RSV) which is the major cause of bronchiolitis and pneumonia in infants and children.

The parainfluenza viruses are the second most common causes of respiratory tract disease in infants and children. They can cause pneumonia, bronchitis and croup in children and the elderly.

Human metapneumovirus, initially described in about 2001, is also implicated in bronchitis, especially in children.

Paramyxoviruses are also responsible for a range of diseases in other animal species, for example canine distemper virus (dogs), phocine distemper virus (seals), cetacean morbillivirus (dolphins and porpoises) Newcastle disease virus (birds) and rinderpest virus (cattle). Some paramyxoviruses such as the henipaviruses are zoonotic pathogens, occurring naturally in an animal host, but also able to infect humans.

................................................................................................................
 
From our Australian friends....
 
 
TECHNOLOGY -
NEW UNDERSTANDING AND NEW TOOLS
 
Future research and development will yield medical and public
health innovations to support improvements in disease control.
Biomedical science is providing new vaccines and other molecular tools
for the prevention, diagnosis and treatment of communicable disease.
New insights are flowing from reading the DNA or RNA sequences
of microbial genes, and from the knowledge this gives about the
protein antigens and enzymes that help the microbe to invade.
 
New techniques can even ‘knock out’ Gene-based approaches to antimicrobial discovery are now concentrating on understanding more
about the organism, its genetic material and its chemical pathways
rather that simply screening thousands of compounds for
their ability to kill microbes.
 
Useful new agents for treatmentmay have effects on RNA or DNA or the pathways for making cell constituents. New studies of bacterial communication via small signal molecules known as ‘pheromones’ also hold promise.
If scientists can understand the natural signals that trigger microbial
multiplication and virulence, they may be able to provide artificial
signals that will permanently switch off the growth of pathogens, and
provide new tools for diseasecontrol.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote KOMET163 Quote  Post ReplyReply Direct Link To This Post Posted: June 10 2006 at 3:24pm
WEll, this means that the monster has come out of pandora's box and has made it's presence known. I hope to god the indoeasians realize that they have doomed a large percentage of the world's popluation to a risk of death.  Maybe they better start praying to allah.  It wont really help much....
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WITHIN LENGTHY POSTS WITHIN THIS LENGTHY THREAD ARE BURIED THESE TWO BRIEF NOTES:

"A Nature report, by Declan Butler, says the virus samples from both Turkish patients have a mutation in the polymerase protein, which serves to replicate the virus's genetic material. The change is a substitution of lycine for glutamic acid at position 627. The same mutation has been seen before, including in Eurasian poultry recently and in the one person who died in the 2003 outbreak of H7N7 avian flu in the Netherlands.

"The polymerase mutation is one of the ten genetic changes that gave rise to the 1918 pandemic flu virus," the story says. The mutation indicates adaptation to humans, said Alan Hay, director of the WHO flu laboratory at the NIMR, as quoted in the story.

"The story goes on to say that the Turkish samples are the first in which the polymerase and hemagglutinin mutations have been found together. "They could make it easier for humans to catch the virus from poultry," it says. "But they might also favor human-to-human transmission." Together, the two mutations help the virus survive and infect cells in the nose and throat, increasing the chance that coughing would spread it via droplets, the story says.

"However, Hay said it is hard to predict how the mutations will affect the virus's behavior and that   'JUST TWO CHANGES ARE UNLIKELY TO CREATE EFFICIENT HUMAN-TO-HUMAN TRANSMISSION ON THEIR OWN,' according to the report."

AND

"LOS ANGELES, May 2 (Xinhua) -- A commercially developed vaccine has successfully protected mice and ferrets against the highly pathogenic H5N1 avian influenza virus, U.S. scientists reported on Tuesday.

    "THE VACCINE, developed by Vical Incorporated in San Diego, California, is also EFFECTIVE AGAINST MULTIPLE HUMAN and bird influenza strains, according to researchers at the ST. JUDE CHILDREN'S RESEARCH HOSPITAL in Memphis, Tennessee, where the animal test was conducted.

    "This finding suggests that such a vaccine WOULD PROTECT humans against multiple variants of the bird and human influenza viruses, SAID RICHARD WEBBY, THE DOCTOR WHO LED THE STUDY.

    "SUCH A VACCINE COULD PROTECT HUMANS AGAINST AN H5N1 'BIRD FLU' VIRUS THAT MUTATES SO THAT IT ADAPTS TO HUMANS and can readily spread from person to person, Webby said. Flu experts and public health officials fear that such an H5N1 variant would trigger a worldwide human flu epidemic."

THE FIRST NOTE STATES THAT THE MUTATIONS DISCUSSED IN THIS THREAD ARE UNLIKELY TO CREATE EFFICIENT HUMAN-TO-HUMAN TRANSMISSION ON THEIR OWN. THIS IS INFORMATION FROM A "NATURE" ARTICLE FROM JANUARY ENTITLED "PANIC OVER BIRD FLU PANDEMIC PREMATURE". THE QUOTE IS FROM "HAY", WHO IS DR. ALAN HAY OF THE NATIONAL INSTITUTE FOR MEDICAL RESEARCH AND ONE OF THE MOST INFORMED EXPERTS WORKING ON BIRD FLU.

THE SECOND NOTE REPORTS THE DEVELOPMENT OF A VACCINE EFFECTIVE AGAINST MUTATIONS THAT WOULD OTHERWISE THREATEN HUMANS AND IS MORE RECENT INFORMATION AND VERY VERY GOOD NEWS BECAUSE IT COMES FROM ST JUDE CHILDRENS RESEARCH HOSPITAL WHICH IS ONE OF THE MOST RESPECTED MEDICAL RESEARCH CENTERS.


Breathe Out, Breathe In, repeat as necessary,
kevin
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Kevin,
 
I wish it was so simple as reading an older article that mention one old strain from Turkey.  And I wish that we could be sure that trials on mice would certainly translate to being effective on humans. 
 
Then there is the problem... in which one of the above articles expounded the following"
 
"Thus, genetic analysis of H5N1 viruses isolated from birds and humans in Hong Kong suggests that these viruses are inherently highly variable and prone to rapid change.
 
The samples were collected and isolated within a single year in the same geographical location and the 6 H5N1 samples had high nucleotide and amino acid variation among the internal genes ." 
 
The vaccine cited; uses these internal genes and they to... are changing rapidly!
 
This same study showed that in a very short time and in a very small area it had recombined (what laymen might call mutated) with virus from chickens; turkeys; ducks; equine(horses); swine(pigs); and fowl
 
This means that it is changing or mutating rapidly... even in small areas.
 
Another change that this article did not mention... because maybe the strain reported in this article did not have this change or the scientist had failed to look for this new change... which is changed receptor specificity to humans. 

So that means if the report has been proven accurate by peer review with other scientist... the virus has gone from being preferential to birds... to now having preference for humans respiratory tracts. (receptor 2,6)

"11 among them had spesifisitas the receptor 2,6. Meaning that, these viruses had the capacity immediately could infect humankind without must from the poultry before."
 
Scientist still do not know what each of these new changes appearing frequently mean... and many of these new changes/strains have not been detected or documented.
 
In addition the lysine substitution at position 627 of PB2 cited in the article allows the H5N1 virus to replicate in a variety of organs, producing systemic infection. This makes it a much more serious infection; resulting in high mortality rates .
 

What makes E627K dangerous?
http://realage.typepad.com/avian_flu/2006/05/anniversary.html

"Human influenza viruses do not spread in birds, and bird influenza viruses generally do not cause disease in humans. (Beare & Webster, 1991)[4] One reason is that typical bird flu viruses need temperatures of about 40 – 41 degrees Celsius to replicate. These temperatures are normal in bird intestines, the typical site of infection in birds. Human influenza viruses are adapted to a lower temperature range, down around 33 degrees Celsius, which is typical for the human upper respiratory tract. The PB2 gene contains instructions for making copies of the virus, and the instruction located at the 627 th  amino acid helps determine at which temperatures this replication functions best. (Massin et al, 2001)[5] 

The E627K version of PB2 is found in human H1, H2, and H3 flu virus strains where it supports faster replication at low temperatures. After Qinghai, the E627K mutation shows up regularly in the H5N1 bird flu strain that has migrated with wild birds westward to Europe and Africa.

 
When mammals get infected with this strain, the disease is more serious than with H5N1 infections that do not have the E627K mutation."
 
We on these boards do not have all the information or training to know exaxtly what we are up against.  And unfortunately the experts are learning and do not have access to all the information or support they need to get the job done.
 
We still do not have a vaccine for aids... another virus inherently highly variable and prone to rapid change."
 
I am afraid there are no easy answers... we simply do not have all the facts.  I tried to give you as many as I thought some might understand... to help give you a global understanding of the many aspects that need to be taken into account.
 
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Thank you, Jhetta; that was generally quite lucid. 

Not to be obnoxious, but does "spesifisitas" mean anything, or is it a product of a translation machine?  It doesn't appear to be Latin...
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Jhetta,

I appreciate your efforts to supply accurate information. However, quite a bit of what is written in this thread and in many others is a confusing, innaccurate, and sometimes hateful mixture of different stories and speculations. Sometimes it seems like a good idea to return focus to the facts.

In this case, the only supposedly new piece of info in this thread is from a blog commentary that claims to quote from a poor translation of one interview with a single researcher:

"11 among [100 samples] had spesifisitas the receptor 2,6. Meaning that, these viruses had the capacity immediately could infect humankind without must from the poultry before."

This commentary also asserts that this research was performed three or four months ago and notes that the virus samples may not be H5N1 (bird flu).

So:

IF, in fact, the virus samples were H5N1 (bird flu), AND IF the results are accurate, THEN the intervening three to four months signifies that this mutation (2,6) is very probably NOT sufficient to cause pandemic.

Other posts in this thread about other mutations date back five months, and so, again, time has shown that there was and is no reason to panic.

Moreover, the post above about a new and very possibly effective bird flu vaccine is recent and wonderful news. I also very much appreciate Anharra's post about emerging science. I have great hope that within two years I'll be donating my emergency food stores to the community homeless shelter.

Exhale, inhale, repeat as necessary,
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Originally posted by kparcell kparcell wrote:

Jhetta,

I appreciate your efforts to supply accurate information.

However, quite a bit of what is written in this thread and in many others is a confusing, innaccurate, and sometimes hateful mixture of different stories and speculations. Sometimes it seems like a good idea to return focus to the facts.

Exhale, inhale, repeat as necessary,
kevin
 
Originally posted by Zondar Zondar wrote:

Thank you, Jhetta; that was generally quite lucid

Not to be obnoxious, but does "spesifisitas" mean anything, or is it a product of a translation machine?  It doesn't appear to be Latin...
  
Aren't you two nice!
 

Based on your response Kevin; maybe I should invest in Vical... they actually have some positive data on a Phase 1 human trial for a vaccine for Ebola. 
 
While I wish Vical and St Jude very good results and I believe the work is important, justified etc.; unfortunately I am a little more jaded.  I prepared info to acquire grants for research in murine (mouse) models... managed the labs that performed the research and help prepare press releases to present this data. I also worked in the invertor relations division of a large company and I fully understand that it is not wise for researchers to bite the hand that funds thier work. I understand that results that look very promising in an non human model do not necessarily translate to good results in a human model.

Ebola DNA Vaccine Produces Immune Responses In All Fully Vaccinated Volunteers In Phase 1 Trial
http://www.medicalnewstoday.com/medicalnews.php?newsid=38203

 
 
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I was worried my post might look like a back-handed compliment, Jhetta.  I didn't mean it to be.
 
"Lucid"--for me, at least--is very high praise to bestow on a piece of writing less than a page long addressing a subject as technical as laboratory virology.
 
It was the "quite," wasn't it?  Makes it seem kind of sniffy and unimpressed.  I didn't want to be critical, but I had to qualify my "lucid" because I thought there were too many unclear (unnecessary?) technical terms, and I found the multi-color text a bit confusing (Is red more important than orange?  Which shade of red?).
 
I'm also a bit of a word maven, and was genuinely curious what the intriguing "spesifisitas" meant.  Webster's was stumped, which only further aroused my curiosity...
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Jhetta,
 
I'm sure that I can speak for many of us on the forum (myself included) who appreciate your hard work and willingness to share (and explain) data.  I'm in healthcare but it's been many years since virology/pathophys/biochem lectures and I've forgotten a lot of it.  So your expertise is greatly appreciated.
 
Please keep up the good work!
K.
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specificity

The ability of the immune response  to interact with individual antigens.

Retrieved from "http://www.biology-online.org/dictionary/Specificities"


Jhetta, I appreciate your work too. We need to be able to discuss these things so we can understand them.

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Thank you, aurora, but it was the novel "s" at the c1 cleavage site of "specificity" that caught my attention, and the altered "as" on the y receptor binding domain.
 
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Dumb question - why hasn't the WHO upped the level to at least 4 with the family clusters in Indonesia?  this would at least cause some concern amongst people who aren't tracking this and they would possibly begin to prep.
 
Jhetta...what is it that you do for a living?  I'm sure you've been asked this before but i've lost track on this site...so many posts.
 
Between you, Albert & Joe - we should all be able to know when to lock ourselves in the house?  that is my ultimate goal for my family and I'm not an expert in ANYTHING - I just want that one answer more than anything else I've gotten (and some great things at that) from all of the folks here.
 
Thank you.  I know more many of us will be looking to you and others for direction.
 
 
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Originally posted by Nikita Nikita wrote:

Dumb question - why hasn't the WHO upped the level to at least 4 with the family clusters in Indonesia?  this would at least cause some concern amongst people who aren't tracking this and they would possibly begin to prep.

Not a dumb question. In fact, that may be the most important question.

There are economic repercussions of Phase 4 which seem to be paramount in the minds of those responsible for determining the level of threat. Money trumps truth every time.

Red
If all is not lost, where is it?
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Kataku™ Automatic Translation Demonstration
This free service enables you to translate English to Indonesian and Indonesian to English, up to 300 words.

http://www.pikiran-rakyat.com/cetak/2006/062006/08/1101.htm

Flu of Burung
 Teka
Teki gazed at the Pandemic Although officially the spread antarmanusia in the level kluster still became the mystery, spesifitas the receptor alfa 2,6 that enabled the bird flu virus to move from humankind to humankind has been found.

Must be attentive seriously so that the pandemic that usually claims many casualties could be avoided.

The influenza VIRUS H5N1 the first time infecting humankind in Hong Kong in 1997.

In December 2003 began to be determined this virus infection in humankind that had contact with the poultry was sick.
A official from the Health Service of the Bandung City took the sample of blood from one of the patient's neighbours "suspect" bird flu, the RN (22 months), in the Cigagak Kel Village.
Cipadung Kec.

Cibiru the Bandung City, on Monday (27/2).
M. the SAPTA TUMULT/HOMEWORK Since That Time till June 6 2006 WHO accepted the report 225 cases of the spread of the virus H5N1 with 128 died in 10 Asian countries, Africa as far as Europe.

Indonesia was in the second level of the number of most cases in the world after Vietnam with 49 cases and 37 died. From 49 patients who it was confirmed were infected by the bird flu virus, 17 among them was in the West Javanese Province. As many as 15 people from 49 patients died.

Now from 17 patients in West Java, seven including being treated in the Handsome Sadikin Hospital (RSHS) Bandung, two people were stated recovered.

Saw this reality, did at this time the world head the new pandemic?
The organisation of the health of the world (WHO) stated the spread of bird flu at this time was to stage 3: pandemic alert.
Meaning that, has had the infection in humankind but was not yet proven had the spread antarmanusia. Needed two stages more before being categorised experienced the pandemic.

The stage 4 was proven had the spread antarmanusia in the group (cluster) small and the stage 5 spreads antarmanusia in the big group (larger). The world had experienced three influenza pandemics in this age.
Spanish influenza happened in 1918 that killed 40-50 million people all over the world.

Asian influenza in 1957 killed 2 million world's populations and Hong Kong influenza (1968) with 1 million fatalities. The pandemic happened when emerging a new virus and spread semudah normal influenza. The chairman Tim the Control of Bird Flu of RSHS Bandung, Dr. Hadi Jusuf Sp.

P. D (K), KPTI mentioned the condition as "spreading semudah normal flu by sneezing and deadly was as cruel as bird flu".
Dr. drh.

C. A. Nidom, M. Sc, the researcher of the bird flu virus from the University of Airlangga Surabaya, said the spread of bird flu antarmanusia very possibly happened.

Was based on the research that the implementation since last March 2006, spesifitas the receptor alfa 2,6 available to humankind could spread antarmanusia.

And spesifitas the receptor has been found in the field (read: the special interview). (link not found)

Moreover the characteristics of this virus really were easy to adapt and stable in the human body.

Nidom had in fact carried out the isolation and results not all that was infected by this virus experienced was sick.

"Therefore, I had the hypothesis if the Jakarta citizen was done surveilans by means of isolating the virus (not the antibodies test), not not all that the figure 70% brought this virus without caused was sick."

I believed that Jakarta was the epicentre of bird flu.

For Bandung, only gods that knew, he said.The matter of the spread antarmanusia in the group (kluster), also still became the mystery.
The case kluster that it was reported happened in the Sembilang Fortification Village, the Subdistrict of three bows, the Regency Karo the North Sumatran Province was that biggest in the world till at this time. Nine people who had affinity relations were infected by the bird flu virus and 7 including dying.

WHO said continued to research the possibility of the spread of bird flu antarmanusia in Indonesia including the existence kluster this.
The statement was hurriedly denied Menkes RI, Siti Fadilah Supari and the Director General of the Control of the Illness and environmental Sanitation Department of Health RI I Nyoman Kandun.

Since July 2005 Indonesia had six cases kluster.

"According to me, something that naive if the number cluster that happened already a large number of in Indonesia and the form of the virus already 2,6 still was said the spread did not happen antarmanusia and still was said only tertular from the poultry," said Nidom
.

Slow him the handling of the government especially in the poultry breeding arrangement was said by Nidom to one of the starting points continued to expand him this illness.

As far as this is concerned, apparently the handling in the sector of poultry breeding still was reactive including the clear rule lack about the vaccine that was used.

Up to the middle of this year, has 19 regencies/the city in West Java that his poultry tertular the bird flu virus.

Six regencies/the other city was threatened because was pressed by the area was infected.

Drh.
Sri Mudjiartiningsih from Labkesda West Java in the training of coverage of bird flu that was spread out by Internews acknowledged the indolence.
According to the veterinary surgeon who had been treated as suspect this bird flu, the handling that did not touch the community happened because of his motor only the Service of province Livestock Breeding.

"Disnak the regency/the city did not have the colleague's fund for that," he said.

The matter of the vaccination also did not yet spread everywhere was done.

In fact, the poultry that has divaksin then only had maximal optimal immunity four months.

That was significant, the vaccination must be repeated routinely minimal three times in a year.

"Must him together like the PIN," he said again. Apart from the vaccine H5N1, to the front Disnak will also use the vaccine H5N2.

The same vaccine kind that currently often is worn by the poultry breeding industry in the homeland.

The matter, Nidom also commented loud.
According to him, the vaccine that was used must be matched with the available virus in the field. "If the available virus in the field was the virus H5N1 that seed the vaccine, yes must H5N1."

Except if indeed has changed his virus, his vaccine must then change.
Likewise seed the vaccine vaccine must be always controlled, he said.Government indolence was also observed in the insignificance of the socialisation against the community.

Blocked (35) villagers Cinunuk the Bandung Regency that lost his two nephews of AT (10) and AC (18) that was stated positive bird flu, claimed confused.

He admitted to not knowing the characteristics of the poultry that was infected by bird flu and the sign of the deadly illness.

"If from the beginning knew his sign like that, let alone having nine chickens that died, definitely we anticipation," he said.

In fact, the distance of the residence Block and the NY family.
C that his two sweethearts were "achieved by" bird" flu with the village office and the community health centre not more than 15 trip minutes by the taxi bike.

But, knowledge concerning the illness that diributkan all the worlds were not obtained by them.

Various bitter realities that happened ought to make the government more efficient took the step.

The sector arrangement of poultry breeding, the comprehensive research with the sample 49 positive cases available until giving the upper answer of millions of the community's questions.The occurrence opportunity of the spread antarmanusia with the discovery spesifitas the receptor alfa 2,6 in the field, the number of cases kluster, pointed out the pandemic already in front of the eyes.
 
Would and when the pandemic happened, indeed could not be predicted.
If in the pandemic beforehand the virus surrounded the earth in time 6-9 months together with the international trip through the ship.

WHO said, it was at this time not impossible for the virus to be able to spread faster in fact infected all the continents only in three months.
Saw the history, the death rate for the pandemic really varied depended the number of people that was infected, the virulence of the virus, the character, and the sensitivity was infected from the population and the effectiveness from the step in the prevention.

So, before the report on the case from 10 countries changed to the pandemic, let's began to do the prevention.

(Wilda Nurlianti/HOMEWORK)
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Nikita,
 
I no longer work in research and have not for 3 years!  We did research with leukemia, thalassemia and murine(mouse) stem cells.
 
 
Thanks Kr105 an aurora :)
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Jhetta,
I just want to thank you as well. You have been tireless and determined to bring information to this forum, and then break it down into laymans terms so that the majority of us who are not in the medical field can understand it. I look forward to your posts for information I can use. Thanks again & KEEP POSTING!Clap
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Jhetta Quote  Post ReplyReply Direct Link To This Post Posted: June 12 2006 at 8:54am
Originally posted by jo007athome jo007athome wrote:

Jhetta,
I just want to thank you as well. You have been tireless and determined to bring information to this forum, and then break it down into laymans terms so that the majority of us who are not in the medical field can understand it. I look forward to your posts for information I can use. Thanks again & KEEP POSTING!Clap
 
Thanks jo007, it is nice to be appreciated :)
 
Here is an article I found on harvard.edu.... I think I will subscribe to Nature... they seem to have the best information out there.  There has been a documented sequence with SA 2,6Gal recognition.
 
Influenza virus receptors in the human airway
Note: The PDF version is much easier to read and has photos and illustrations.

Vol 440|23 March 2006

"It is interesting that the A/Hong Kong/213/03 (H5N1) virus, which was isolated from a human and recognizes both SA 2,3Gal and SA 2,6Gal....
 
...unimpeded transmission of the virus might require acquisition of the ability to recognize SA 2,6Gal. This change would enable the virus to replicate in the upper region of the respiratory tract, where it could be readily spread by sneezing and coughing.
 
Mutations in the viral haemagglutinin molecule would be necessary to confer SA 2,6Gal binding ability on H5N1 avian viruses, although amino-acid substitutions in other viral pro-teins, including PB2 (refs 7, 8), may be required to confer pandemic potential on avian viruses that can efficiently replicate in humans. "

Influenza virus receptors in the human airway Avian and human flu viruses seem to target different regions of a patient’s respiratory tract. Although more than 100 people have beeninfected by H5N1 influenza A viruses, human-to-human transmission is rare1.
 
What are the molecular barriers limiting human-to-humantransmission? Here we demonstrate ananatomical difference in the distributionin thehuman airway of the different binding mol-ecules preferred by the avian and human influenza viruses. The respective molecules are sialic acid linked to galactose by an -2,3linkage (SA 2,3Gal) and by an -2,6 linkage(SA 2,6Gal)2. Our findings may provide arational explanation for why H5N1 viruses at present rarely infect and spread between humans although they can replicate efficientlyin the lungs. SA 2,3Gal molecules have been found on cells artificially differentiated from isolated human tracheal and bronchial cells in vitro3. But the anatomical distribution and preva-lence of SA 2,3Gal and SA 2,6Gal in the human airway was unknown. Using lectinsspecific for SA 2,3Gal and SA 2,6Gal, we found that SA 2,6Gal is dominant on epi-thelial cells in nasal mucosa, with SA 2,3Galbeing occasionally detected (for details and methods, see supplementary information).Epithelial cells in the paranasal sinuses, thepharynx, the trachea4and the bronchi mainly express SA 2,6Gal In the terminal andrespiratory bronchioles, epithelial cells also express SA 2,6Gal sialyloligosaccharides. SA 2,3Gal was found on non-ciliatedcuboidal bronchiolar cells at the junction between the respiratory bronchiole and alveo-lus, however, and a substantial number of cells lining the alveolar wall also expressed this mol-ecule. The SA 2,3Gal-positive alveolar cells also reacted to an antibody against surfactant protein A; this suggests that they were alveolar type-II cells (which express surfactant proteinA). Alveolar type-II cells have been shown to be infected with H5N1 virus in a patient5. Human-derived viruses that preferentially recognize SA 2,6Gal bound extensively to epithelial cells in the bronchi and, to a lesser degree, to alveolar cells; by contrast, avian viruses that preferentially recognize SA 2,3Gal bound extensively to alveolar cells but less widely to bronchial epithelial cells (see supple-mentary information). It is interesting that the A/Hong Kong/213/03 (H5N1) virus, which was isolated from a human and recognizes both SA 2,3Gal and SA 2,6Gal (ref. 6), bound BRIEF COMMUNICATIONS Figure 1 | Reactivity of human respiratory tissues with lectins specific for different sialic acid linkages.a, Nasal mucosa; b, paranasal sinuses; c, bronchus; d, bronchiole; e, alveolus. Res, respiratory bronchiole (adjacent to alveoli); Ter, terminal bronchiole (distal to alveoli); Alv, alveolus. Green,reaction with Sambucus nigra lectin, indicating the presence of sialic acid linked to galactose by an 2,6-linkage (SA 2,6Gal). Red, reaction with Maackia amurensis lectin, indicating the presence of SA 2,3Gal. Cells were counter stained with DAPI (4,6-diamidino-2-phenylindole). abcedTerResAlv Figure 2|Infection of human respiratory tissue by influenza A viruses. a, Extensive infection of bronchial epithelial cells by human A/Kawasaki/173/01 (H1N1) virus. b,Infection of alveolar cells by the human virus.c, Bronchial epithelial cells are not infected byA/duck/Mongolia/301/01 (H3N2) virus. d,I nfection of alveolar cells by the avian virus. The results obtained with other human viruses, A/Yokohama/2057/03(H3N2) and A/Kawasaki/176/02 (H1N1), were similar to those obtained with A/Kawasaki/173/01, and those obtained with the avian viruses A/duck/Czechoslovakia/56 (H4N6) and A/duck/Vietnam/5001/05(H5N1) were similar to those obtained with A/duck/Mongolia/301/01. Infected cells are stained brown extensively to both bronchial and alveolar cells. Human-derived viruses preferentially rec-ognizing SA 2,6Gal efficiently infected epi-the lial cells lining the bronchi and alveolar cells (Fig. 2a, b), whereas avian viruses prefer-entially recognizing SA 2,3Gal infected alve-olar cells but not bronchial epithelial cells (Fig. 2c, d, and see supplementary informa-tion). As shown in a virus-binding assay,A/Hong Kong/213/03 infected both alveolar cells and epithelial cells in bronchi (see supple-mentary information). Although not quanti-tative, these results indicate that there could be functional significance in the preferential expression of SA 2,3Gal and SA 2,6Gal mol-ecules on human airway cells.
 
Our findings indicate that although H5N1 viruses preferentially recognizing SA 2,3Gal can be transmitted from birds to humans, they can replicate efficiently only in cells in the lower region of the respiratory tract, where the avian-virus receptor is prevalent.

This restriction may contribute to the inefficient human-to-human transmission of H5N1 viruses seen so far, and indicates that unimpeded transmission of the virus might require acquisition of the ability to recognize SA 2,6Gal. This change would enable the virus to replicate in the upper region of the respiratory tract, where it could be read-ily spread by sneezing and coughing.
 
Muta-tions in the viral haemagglutinin molecule would be necessary to confer SA 2,6Gal-bind-ing ability on H5N1 avian viruses, although amino-acid substitutions in other viral pro-teins, including PB2 (refs 7, 8), may be required to confer pandemic potential on avian viruses that can efficiently replicate in humans.
 
Kyoko Shinya*†‡§, Masahito Ebina||, ShinyaYamada†, Masao Ono¶, Noriyuki Kasai‡,Yoshihiro Kawaoka*†#✩*Department of Pathobiological Sciences, Schoolof Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USAe-mail: kawaokay@svm.vetmed.wisc.edu†Division of Virology, Department ofMicrobiology and Immunology, #InternationalResearch Center for Infectious Diseases, Instituteof Medical Science, University of Tokyo,Tokyo 108-8639, Japan‡Institute for Animal Experimentation,||Respiratory Oncology and Molecular Medicine,Institute of Development, Aging, and Cancer,in 1998 (ref. 5), in 2002 (ref. 5) and in 2003(ref. 6), respectively.
 
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Jhetta Quote  Post ReplyReply Direct Link To This Post Posted: June 12 2006 at 12:51pm

Fluprepper found this and posted it in another thread very interested info cited as coming from WHO.

Hemispherx Biopharma Advances Influenza Vaccine/Immunopotentiation Clinical Trials Designed to Increase Vaccine Dosage Supply and Increase Cross-Protection; Australian Clinical Protocol Complete

6/12/2006 8:30:00 AM EST

BIOWIRE

Hemispherx Biopharma, Inc. (AMEX: HEB) announced that the Company had completed final design of a well-controlled, Ampligen(R) vs. placebo, immunopotentiation trial of seasonal influenza vaccinations. The design follows closely newly published FDA guidelines for determining potential efficacy. The clinical study seeks to extend the findings from the preclinical models, including primates, being conducted in collaboration with the Japanese National Institute for Infectious Diseases, to determine the extent to which Ampligen(R) may increase the effectiveness of vaccines and thereby broaden the availability of flu vaccine doses to treat more at-risk groups, such as senior citizens.

Ongoing preclinical studies suggest that Ampligen(R), an experimental immunotherapeutic for which an NDA is being prepared for chronic fatigue syndrome (CFS), may achieve two major therapeutic benefits when co-administered with influenza vaccines. First, in studies conducted by the Japanese National Institute of Infectious Diseases (JNIID), protective antibody levels increased up to 100-fold against seasonal influenza viruses. Second, using highly pathogenic lethal avian influenza viruses (HPIV) JNIID found that when co-administered with HPIV vaccines, Ampligen(R) provided cross-protection against variant HPIV strains 100-300 fold.

These are the first scientific reports of potentiation and cross-protection of this magnitude with human or avian influenza viruses.

Variant HPIV has recently been isolated in Indonesia, and may account for the relative ineffectiveness of current vaccines. Specifically, the World Health Organization (WHO) has also noted the increased level of H5N1 in the patients' throat, which is a property associated with more efficient transmission of the virus, and may account for the 100% death rate recently in an Indonesian village.

Indonesian H5N1 deaths averaged one human bird flu death every 2.5 days in May. There are growing concerns for increased bird flu deaths in the wake of the recent earthquake.

Hemispherx Biopharma's clinical programs in flu vaccine use are designed to eliminate and/or mitigate the growing vaccine supply problems and to make the existing vaccines more effective in combating a potential pandemic. Success in this arena will require novel immunological strategies not part of the traditional worldwide vaccine procurement programs.

About Hemispherx

Hemispherx Biopharma, based in Philadelphia, is a biopharmaceutical company engaged in the manufacture and clinical development of new drug entities for treatment of viral and immune-based disorders. Hemispherx Biopharma's flagship products include Alferon(R) and the experimental immunotherapeutics/antivirals Ampligen(R), Alferon LDO and Oragens(TM). Alferon(R) is approved for a category of STD infection, and Ampligen(R) and Oragens(TM) represent experimental nucleic acids being developed for globally important viral diseases and disorders of the immune system. Hemispherx's platform technology includes large and small agent components for potential treatment of various viral infections. Hemispherx has in excess of 100 patents comprising its core intellectual property estate, a fully commercialized product (Alferon(R) N) and GMP certified manufacturing facilities for its novel pharma products. For more information please visit www.hemispherx.net

Information contained in this news release other than historical information, should be considered forward-looking and is subject to various risk factors and uncertainties. For instance, the strategies and operations of Hemispherx involve risk of competition, changing market conditions, change in laws and regulations affecting these industries and numerous other factors discussed in this release and in the Company's filings with the Securities and Exchange Commission. Any specifically referenced investigational drugs and associated technologies of the company (including Ampligen(R), Alferon(R) LDO and Oragens) are experimental in nature and as such are not designated safe and effective by a regulatory authority for general use and are legally available only through clinical trials with the referenced disorders. The forward-looking statements represent the Company's judgment as of the date of this release. The Company disclaims, however, any intent or obligation to update these forward-looking statements. Clinical trials for other potential indications of the approved biologic Alferon(R) do not imply that the product will ever be specifically approved commercially for these other treatment indications.

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Guests Quote  Post ReplyReply Direct Link To This Post Posted: June 12 2006 at 3:08pm
It annoys me when avianflutalk pretends that we are the only forum on the web discussing this.  Why are the links to other web sites always altered so as to be unreadable?  In the top article about Dr. Niman's article, it is not possible to find out more.  I'm going to research the other web forums to see if they engage in this practice.   I'd rather participate in a discussion that allows references to where the information was obtained.  Or post a rule, DO NOT MENTION anything you heard on one of our competitors!  That would be more honest.
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