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**gsgs** · October 27, 2007, 03:26 AM

Re: Neuraminidase Inhibitor-Resistant Recombinant A/Vietnam/1203/04 (H5N1) Flu Viruse

thanks F1 for all those articles !
Where do you find them, is there a recommended list which we
could/should check regularly for new articles ?

Now it's scattered through many FT-subforums, maybe an extra
subforum just listing recent articles or only links to them would be fine ?

Also short summaries, shorter than the abstract and written by
3rd person. Say 5 lines (IMO)
Why doesn't this exist already ? Or does it (in some Journal or webpage...)

**JohnW** · October 27, 2007, 01:36 PM

Re: Neuraminidase Inhibitor-Resistant Recombinant A/Vietnam/1203/04 (H5N1) Flu Viruse

Try this one:

Just a moment...

http://www.sciencemag.org/cgi/alerts

I set my alerts up for "pandemic". Get a lot besides H5N1, but I did get a link to the article mentioned above.

As an aside, is it just me who feels like the findings from recent scientific research have been consistently "bad news"? It seems like nothing cuts down the virulence of this virus! It is adapting to lower temperatures in the host. The human species show both type "3" and "6" scialic acid receptors throughout the body. It is passed from mother to unborn child. It attenuates type I interferon response. etc. etc.

**Anne** · October 27, 2007, 03:38 PM

Re: Neuraminidase Inhibitor-Resistant Recombinant A/Vietnam/1203/04 (H5N1) Flu Viruse

nohing is cutting down the virulence, and this virus has a clivage site ( the 1918 virus did'nt have one )

**tropical** · October 29, 2007, 04:19 AM

Re: Neuraminidase Inhibitor-Resistant Recombinant A/Vietnam/1203/04 (H5N1) Flu Viruse

Very bad news. Than, the "only", or near way of blocking (blanketing) a begining of a pandemic, or to slow it, start to fail!<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /><o:p></o:p>
<o:p></o:p>
"Our results suggest that NA inhibitor-resistant H5N1 variants may retain the high pathogenicity of the wild-type virus in mammalian species."<o:p></o:p>
<o:p></o:p>
This mean that a CFR can remain 80% like in Indo.<o:p></o:p>
I don't understand why than the drills concentrate on CFR=2%?<o:p></o:p>
Maybe that tacitly confirm that with CFR>50% we have no way to organize anithing...<o:p></o:p>
<o:p></o:p>
The only hope seems to remain the cold-dry versus hot-wet hypothesis in a FT thread:<o:p></o:p>
"Why no Pandemic Wildfire Yet? An Hypothesis. - from Monotreme",<o:p></o:p>
that a pandemic will not start because we have a global warming.<o:p></o:p>
Still, we have other bugs recrudescences, seasonal flu, and other respiratory virus mutations (all natural?).<o:p></o:p>

**AlaskaDenise** · November 4, 2007, 03:47 AM

Re: Neuraminidase Inhibitor-Resistant Recombinant A/Vietnam/1203/04 (H5N1) Flu Viruse

This mean that a CFR can remain 80% like in Indo.<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /><o:p></o:p>

Remember that the surviving 20% survive because of appropriate medical treatment, which will be available to a pittance of the population during an actual pandemic (that's assuming the pandemic version isn't anti-viral resistant).

One number that hasn't changed is the CFR for those NOT receiving appropriate medical care (which may be prevalent during a pandemic). That number is.......100%.

One number that is an unknown is the infectivity rate. History says about 25- 40%, but hopefully this crazy H5N1 will be lower.

We're all hoping for........time. Time to make more antivirals, time to develop a good prepandemic vaccine, time to build high-volume vaccine plants, etc.

.

**HenryN** · November 4, 2007, 03:50 AM

Re: Neuraminidase Inhibitor-Resistant Recombinant A/Vietnam/1203/04 (H5N1) Flu Viruse

Originally posted by Florida1 View Post

Neuraminidase Inhibitor-Resistant Recombinant A/Vietnam/1203/04 (H5N1) Influenza Viruses Retain Their Replication Efficiency and Pathogenicity In Vitro and In Vivo

Hui-Ling Yen, Natalia A. Ilyushina, Rachelle Salomon, Erich Hoffmann, Robert G. Webster, and Elena A. Govorkova*

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794
Received 17 May 2007/ Accepted 29 August 2007
Effective antiviral drugs are essential for early control of an influenza pandemic. It is therefore crucial to evaluate the possible threat posed by neuraminidase (NA) inhibitor-resistant influenza viruses with pandemic potential. Four NA mutations (E119G, H274Y, R292K, and N294S) that have been reported to confer resistance to NA inhibitors were each introduced into recombinant A/Vietnam/1203/04 (VN1203) H5N1 influenza virus. For comparison, the same mutations were introduced into recombinant A/Puerto Rico/8/34 (PR8) H1N1 influenza virus. The E119G and R292K mutations significantly compromised viral growth in vitro, but the H274Y and N294S mutations were stably maintained in VN1203 and PR8 viruses. In both backgrounds, the H274Y and N294S mutations conferred resistance to oseltamivir carboxylate (50% inhibitory concentration [IC50] increases, >250-fold and >20-fold, respectively), and the N294S mutation reduced susceptibility to zanamivir (IC50 increase, >3.0-fold). Although the H274Y and N294S mutations did not compromise the replication efficiency of VN1203 or PR8 viruses in vitro, these mutations slightly reduced the lethality of PR8 virus in mice. However, the VN1203 virus carrying either the H274Y or N294S mutation exhibited lethality similar to that of the wild-type VN1203 virus. The different enzyme kinetic parameters (Vmax and Km) of avian-like VN1203 NA and human-like PR8 NA suggest that resistance-associated NA mutations can cause different levels of functional loss in NA glycoproteins of the same subtype. Our results suggest that NA inhibitor-resistant H5N1 variants may retain the high pathogenicity of the wild-type virus in mammalian species. Patients receiving NA inhibitors for H5N1 influenza virus infection should be closely monitored for the emergence of resistant variants. 

<HR align=left width="50%">* Corresponding author. Mailing address: Department of Infectious Diseases, St. Jude Children's Research Hospital,<SCRIPT type=text/javascript></SCRIPT>

 Published ahead of print on 12 September 2007. 
 H.-L. Yen and N. A. Ilyushina contributed equally to this work.

Just a moment...

http://jvi.asm.org/cgi/content/abstract/81/22/12418

H274Y and N294S have been found in avian H5N1, indicating virus with these changes are fit.

N294S Tamiflu Resistance is Evolutionarily Fit

http://www.recombinomics.com/News/01180702/H5N1_Egypt_N294S_Fit.html

Recombinomics Commentary

Suspect H5N1 in Geese in Hungary

http://www.recombinomics.com/News/01220702/H5N1_Hungary.html

Recombinomics Commentary

**AlaskaDenise** · November 4, 2007, 03:54 AM

Re: Neuraminidase Inhibitor-Resistant Recombinant A/Vietnam/1203/04 (H5N1) Flu Viruse

.....indicating virus with these changes are fit.

Translation please.

from "fit" commentary....

this change is not evolutionarily fit

Still don't comprehend.

.

**AlaskaDenise** · November 4, 2007, 04:01 AM

Re: Neuraminidase Inhibitor-Resistant Recombinant A/Vietnam/1203/04 (H5N1) Flu Viruse

Originally posted by niman View Post

H274Y and N294S have been found in avian H5N1, indicating virus with these changes are fit.

N294S Tamiflu Resistance is Evolutionarily Fit

http://www.recombinomics.com/News/01180702/H5N1_Egypt_N294S_Fit.html

Recombinomics Commentary

http://www.recombinomics.com/News/01...1_Hungary.html

Commentary

N294S Tamiflu Resistance is Evolutionarily Fit
Recombinomics Commentary
January 18, 2007

?Given the information we have, we don?t see any broad public health implications,? said Dick Thompson, a spokesman for the organization.
Mr. Thompson was unsure which Egyptian cluster of flu infections the patients were part of. But another source said it was one in Gharbiya Province, roughly 50 miles north of Cairo, in which flu killed three people last month in a 33-member family living in one compound.

Oseltamivir-resistant strains were found in three unrelated patients in Vietnam in 2005 but did not spread.

The above comments on Tamiflu resistance in H5N1 are incomplete. Previously, H274Y has been found in H5N1 patients that have been treated with Tamiflu. However, this change appears to have developed during treatment. It was not detected in initial collections from the patient, or was initially present at low levels. This change is the only prior reported H5N1 oseltamivir resistant change in H5N1 in patients. However, data in the literature on H274Y indicates this change is not evolutionarily fit, and therefore H5N1 with this change has not been islated from sources other than patients undergoing Tamiflu treatment.

However, N294S has been detected previously in H5N1 in ducks in China (A/duck/Zhejiang/bj/2002(H5N1) and A/Duck/Hong Kong/380.5/2001(H5N1)). Both of these isolates were highly pathogenic with the common HA cleavage site, RERRRKKR), but did not have the 20 amino acid deletion, which defines the Z genotype, including the Qinghai strain that is transmitted and transported by migratory birds, including the teal identified in Egypt in December, 2005.

However, N294S has not been previously reported in patients or the Qinghai strain of H5N1. Most of the NA Qinghai sequences have been sequestered in the private WHO database at Los Alamos. This private database is used by Weybridge, who has sequenced a large number of Qinghai isolates in Europe and the Middle East, as well as the CDC in Atlanta, which gets samples from NAMRU-3 in Cairo. Thus, N294S may have already been identified in Qinghai H5N1, but that information is not public.

The presence of N294S in H5N1 in ducks in China however, creates a source for the acquisition of the change via recombination. The presence of N294S in both patients in samples collected within 48 hours of Tamiflu treatment suggests the sequences were present prior to Tamiflu treatment of the three cluster members. All three failed to respond to treatment and died.

More NA sequence data on additional patients and birds in Egypt would be useful.
--------------------------------------
Commentary

Suspect H5N1 in Geese in Hungary
Recombinomics Commentary
January 22, 2007

Five geese found dead in southeastern Hungary are being tested for suspected bird flu, an Agriculture Ministry official said on Monday.

The dead birds are being tested in Budapest and come from a large farm in the southeastern county of Csongrad where about 40 geese had fallen sick and some had died, Farming Ministry Secretary of State Fulop Benedek told national news agency MTI.

Veterinarians who saw the birds said the suspicion of bird flu was justified.

The above comments suggest H5N1 may have been detected in southern Hungary. Although H5N1 has been reported in the Ukraine this season, other countries in Europe have failed to detect or report bird flu for about 12 months. Last season many countries in Europe reported H5N1 in late January and throughout February. This season most of the reports have been out of Africa, in Egypt, Sudan, and Nigeria.

The recent outbreak in Egypt has resulted in the death of all five confirmed cases this season, and the two sequences from the Gharbiya cluster had the Tamiflu resistance marker, N294S. The failure to find wild type sequences for this position strongly suggests the polymorphism was in the H5N1 prior to the start of Tamiflu treatment. Moreover, N294S has also been identified in H5N1 in ducks in China. The acquisition of N294S appears likely. The HA sequences from these patients had a receptor binding site change, V223I, which was detected previously in H5N1 from geese in Shantou. The Gharbiya NA sequence also had a new change, M107I. This polymorphism was in the same Shantou geese that had the V223I change in HA. The presence of two newly acquired polymorphisms in two genes that match a common source strongly supports acquisition of these polymorphisms by recombination.

Such acquisitions are cause for concern. In addition to the N294S polymorphisms in ducks in H5N1 infected ducks in China, the common Tamiflu resistance marker, H274Y, has been detected in Qinghai isolates in Astrakhan (A/swan/Astrakhan/1/2005(H5N1) and A/swan/Astrakhan/Russia/Nov-2/2005(H5N1), raising the possibility of more Tamiflu resistance in the region linked to Qinghai H5N1 infections.

.

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