• FluTrackers.com Inc. does not provide medical advice. Information on this web site is collected from various internet resources, and the FluTrackers board of directors makes no warranty to the safety, efficacy, correctness or completeness of the information posted on this site by any author or poster. The information collated here is for instructional and/or discussion purposes only and is NOT intended to diagnose or treat any disease, illness, or other medical condition. Every individual reader or poster should seek advice from their personal physician/healthcare practitioner before considering or using any interventions that are discussed on this website. By continuing to access this website you agree to consult your personal physican before using any interventions posted on this website, and you agree to hold harmless FluTrackers.com Inc., the board of directors, the members, and all authors and posters for any effects from use of any medication, supplement, vitamin or other substance, device, intervention, etc. mentioned in posts on this website, or other internet venues referenced in posts on this website.
  • We are not asking for any donations. Do not donate to any entity who says they are raising funds for us.

Bird flu mutating to infect people more easily

4-ABBA

Well-known member
Link: http://www.msnbc.msn.com/id/21141012/

Updated: 2 hours, 33 minutes ago
NEW YORK - The H5N1 bird flu virus has mutated to infect people more easily, although it still has not transformed into a pandemic strain, researchers said on Thursday.

The changes are worrying, said Dr. Yoshihiro Kawaoka of the University of Wisconsin-Madison.

"We have identified a specific change that could make bird flu grow in the upper respiratory tract of humans," said Kawaoka, who led the study.

"The viruses that are circulating in Africa and Europe are the ones closest to becoming a human virus," Kawaoka said.

Recent samples of virus taken from birds in Africa and Europe all carry the mutation, Kawaoka and colleagues report in the Public Library of Science journal PLoS Pathogens.

"I don't like to scare the public, because they cannot do very much. But at the same time it is important to the scientific community to understand what is happening," Kawaoka said in a telephone interview.

The H5N1 avian flu virus, which mostly infects birds, has since 2003 infected 329 people in 12 countries, killing 201 of them. It very rarely passes from one person to another, but if it acquires the ability to do so easily, it likely will cause a global epidemic.

All flu viruses evolve constantly and scientists have some ideas about what mutations are needed to change a virus from one that infects birds easily to one more comfortable in humans.

Birds usually have a body temperature of 106 degrees F, and humans are 98.6 degrees F usually. The human nose and throat, where flu viruses usually enter, is usually around 91.4 degrees F.

"So usually the bird flu doesn't grow well in the nose or throat of humans," Kawaoka said. This particular mutation allows H5N1 to live well in the cooler temperatures of the human upper respiratory tract.

H5N1 caused its first mass die-off among wild waterfowl in 2005 at Qinghai Lake in central China, where hundreds of thousands of migratory birds congregate.

That strain of the virus was carried across Asia to Africa and Europe by migrating birds. Its descendants carry the mutation, Kawaoka said.

"So the viruses circulating in Europe and Africa, they all have this mutation. So they are the ones that are closer to human-like flu," Kawaoka said.

Luckily, they do not carry other mutations, he said.

"Clearly there are more mutations that are needed. We don't know how many mutations are needed for them to become pandemic strains."

Copyright 2007 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content is expressly prohibited without the prior written consent of Reuters.
 
Re: Bird flu mutating to infect people more easily

so, it is mutating and the result is, that some mutation(s) is (are)
better adapter to human hosts, while others are worse.

And this is probably coincidentally since it doesn't target the humans,
no chains of transmission,no selection in humans.
Unless there is a mammalean reservoir

What mutation they mean, is it secret ?
[edit:presumably E627K in PB2, see the other thread]

Can that mutation be implemented into the Indo-virus
and tested in ferrets ?
 
Re: Bird flu mutating to infect people more easily

so, it is mutating and the result is, that some mutation(s) is (are)
better adapter to human hosts, while others are worse.

And this is probably coincidentally since it doesn't target the humans,
no chains of transmission,no selection in humans.
Unless there is a mammalean reservoir

What mutation they mean, is it secret ?
[edit:presumably E627K in PB2, see the other thread]

Can that mutation be implemented into the Indo-virus
and tested in ferrets ?
Please. This is NOT a coincidence.

Qinghai H5N1 can be quite lethal, so the E627K keeps the level low, so the H5N1 is easily transported by birds and goes undetected in the dismal surveillance assays of conservation groups who keep insisting that Qinghai H5N1 in wild birds is a minor issue.

H5N1 knows EXACTLY what it is doing, conservation groups and message board nonsense not withstanding.
 
Re: Bird flu mutating to infect people more easily

i presume this isnt good news for us humans.....?.
 
Re: Bird flu mutating to infect people more easily

Commentary on Dr. Niman's commentary at:
www.scottmcpherson.net/journal

Those of us who follow Recombinomics are a) not at all surprised, since Dr. Niman found this a year ago; and b) probably elated that someone else has confirmed his findings. If Dr. Niman had Kawaoka's $9 million facilities.....
 
Re: Bird flu mutating to infect people more easily

Commentary on Dr. Niman's commentary at:
www.scottmcpherson.net/journal

Those of us who follow Recombinomics are a) not at all surprised, since Dr. Niman found this a year ago; and b) probably elated that someone else has confirmed his findings. If Dr. Niman had Kawaoka's $9 million facilities.....

Scott, if you are seriously interested in scholarly research related to this mutation and it affects on avian vs mammalian replication, you may wish to read results form the following study:

"Residue 627 of PB2 Is a Determinant of Cold Sensitivity in RNA Replication of Avian Influenza Viruses "

Received 25 September 2000/Accepted 21 February 2001

http://jvi.asm.org/cgi/content/full...INDEX=0&volume=75&issue=11&resourcetype=HWCIT

By the by, the above research was also confirmation of previous studies conducted in the early 1990s.
 
Re: Bird flu mutating to infect people more easily

By the by, the above research was also confirmation of previous studies conducted in the early 1990s.


So why was the current paper done? What does it add to our knowledge? What are the implications of this research, in practical terms?

J.
 
Re: Bird flu mutating to infect people more easily

To Mamabird:
Thank you for the link! Appreciated.

To Cartski:
Recall this is the same researcher who just got spanked recently for wanting to monkey with Ebola (sorry, no pun intended) in a level 2 biofacility at UW-M. Even though what he wanted to work on was essentially inactive Ebola, the Feds still paled at his request.

Maybe they felt that they needed some good press. As Dr. Niman said: It is not good, but it is not news. Dr. Richard Webby told me,
"But, the PB2 627 residue has been implicated for many years in flu virulence (and even temperature of replication)." So its presence in H5N1 is of concern. Just not news to FT posters!
 
Re: Bird flu mutating to infect people more easily

So why was the current paper done? What does it add to our knowledge? What are the implications of this research, in practical terms?

J.

J, in my view, the research was very well done and thorough. It confirms previous research. In other words, by the fact that the previous experiments were more or less repeatable, the new research validates our understanding of the importance of Lysine at position 627 of the PB2 gene segment. This research also focuses on the H5N1 virus, a hot topic primarily for its high pathogenicity in domestic poultry and mammals.

Unfortunately, the Reuters news release, including statements by the researchers themselves in interviews, led folks to believe that this was a new discovery and a signal event in the evolution of H5N1. Although the acquistion of the Lysine is clearly important, it is certainly not new. Many folks have been tracking its progress across Eurasia and Africa as migratory birds, and perhaps others, have carried the Qinghai strain to unsuspecting farmers and local human inhabitants.

I would end by saying that the researchers reach the correct conclusion in their paper, which is that if we begin to see other human like mutations becoming fixed in these H5, H7 and H9 viruses, in conjunction with E627K, then we need to sit up straight in our chairs and take notice of potential mischief in the near term. All eleven proteins of the Influenza A virus have some highly conserved human markers like this one in PB2. No one really knows how many such changes would be required to make these avian viruses more easily transmittable to and between us humans.
 
Re: Bird flu mutating to infect people more easily

Commentary

E627K Increases H5N1 Replication at Lower Temperatures

Recombinomics Commentary
October 5, 2007

Birds usually have a body temperature of 106 degrees F, and humans are 98.6 degrees F usually. The human nose and throat, where flu viruses usually enter, is usually around 91.4 degrees F.

"So usually the bird flu doesn't grow well in the nose or throat of humans," Kawaoka said. This particular mutation allows H5N1 to live well in the cooler temperatures of the human upper respiratory tract.

H5N1 caused its first mass die-off among wild waterfowl in 2005 at Qinghai Lake in central China, where hundreds of thousands of migratory birds congregate.

That strain of the virus was carried across Asia to Africa and Europe by migrating birds. Its descendants carry the mutation, Kawaoka said.

"So the viruses circulating in Europe and Africa, they all have this mutation. So they are the ones that are closer to human-like flu," Kawaoka said.

Luckily, they do not carry other mutations, he said.

The above comments on the paper describing PB2 E627K replication in experimental mice and cells highlight the effect of the change on the ability of the Qinghai strain to replicate at lower temperatures.

The detection of E627K in dead wild birds at Qinghai Lake in May, 2005 signaled a major change in the global spread of H5N1. At the time ?Asian? H5N1 had not been reported in any country west of China. The massive die-off at Qinghai Lake signaled the movement of H5N1 in long range migratory birds and the strain of a major geographical expansion.

The data on the temperature dependence of E627K also explains why many surveillance programs fail to detect Qinghai H5N1 in live wild birds, including locations where H5N1 is readily detected in dead or dying wild birds. The body temperature of live wild birds keeps the levels of the virus low, below the detection levels of these assays. Dead and dying birds have a lower body temperature, allowing levels of the virus to rise.

Although the effect of E627K on viral replication has been know since 2001, this fact has been ignored in the surveillance programs that focus on live birds. Instead of measuring H5N1 antibody levels, which are more stable and reliable, these groups test thousands of birds and then use the false negatives to issue assurances and denials of the transport and transmission of H5N1 by wild birds.

Consequently, the alarming expansion of Qinghai H5N1 has largely happened below the radar of these surveillance, which remains a cause for concern, as have changes in the receptor binding domain in Qinghai isolates from fatal human cases, including V223I, S227N, and M230I.


.
 
Re: Bird flu mutating to infect people more easily

The body temperature of live wild birds keeps the levels of the virus low, below the detection levels of these assays


Are you saying that the PB2/627K mutation mandates that the virus may ONLY replicate at human temperatures?

I had thought it merely expanded the range of possibilities.

.
 
Re: Bird flu mutating to infect people more easily

So why was the current paper done? What does it add to our knowledge? What are the implications of this research, in practical terms?

J.

Upon reading the webconferences.com presentation, on page 40 there is an interesting chart on "Neutralizing antibodies to a virus with the 1918 virus HA & NA."

Perhaps some of our highly qualified members could comment on why (after many years of being nearly zero) those 1918 antibodies would rise after the 1957 H2N2, 1968 H3N2, and 1979 H1N1 mini-pandemics.

If someone can copy page 40
(http://www.webconferences.com/nihoba/ppt/Biosafety%20final%20Kawaoka.pdf),
it would be helpful.

.
 
Re: Bird flu mutating to infect people more easily

Bird Flu Viruses Found In Africa And Europe 'Closest To Becoming A Human Virus'

http://www.sciencedaily.com/releases/2007/10/071004205327.htm

Science Daily ? Since it first appeared in Hong Kong in 1997, the H5N1 avian flu virus has been slowly evolving into a pathogen better equipped to infect humans. The final form of the virus, biomedical researchers fear, will be a highly pathogenic strain of influenza that spreads easily among humans.

Now, in a new study a team of researchers from the University of Wisconsin-Madison report the identification of a key step the virus must take to facilitate the easy transmission of the virus from person to person.

A team of researchers led by virologist Yoshihiro Kawaoka of the UW-Madison School of Veterinary Medicine has identified a single change in a viral protein that facilitates the virus' ability to infect the cells of the upper respiratory system in mammals. By adapting to the upper respiratory system, the virus is capable of infecting a wider range of cell types and is more easily spread, potentially setting the stage for a flu pandemic.

"The viruses that are in circulation now are much more mammalian-like than the ones circulating in 1997," says Kawaoka, an internationally recognized authority on influenza. "The viruses that are circulating in Africa and Europe are the ones closest to becoming a human virus."

As its name implies, bird flu first arises in chickens and other birds. Humans and other animals in close contact with the birds may be infected, and the virus begins to adapt to new host animals, a process that may take years as small changes accumulate. Over time, an avian virus may gather enough genetic change to spread easily, as experts believe was the case with the 1918 Spanish flu, an event that killed at least 30 million people worldwide.

In the new study, which was conducted in mice, the Wisconsin team identified a single change in a viral surface protein that enabled the H5N1 virus to settle into the upper respiratory system, which "may provide a platform for the adaptation of avian H5N1 viruses to humans and for efficient person-to-person virus transmission."

Other currently undetermined changes are required for the virus to become a human pathogen of pandemic proportions, Kawaoka explains, but establishing itself in the upper respiratory system is necessary as that enables easy transmission of the virus through coughing and sneezing.

To date, more than 250 H5N1 human infections worldwide have been reported. Of those, more than 150 have been fatal, but so far efficient human-to-human transmission has not occurred. Most infections have occurred as a result of humans being in close contact with birds such as chickens that have the virus.

According to Kawaoka, the avian virus can be at home in the lungs of humans and other mammals as the cells of the lower respiratory system have receptors that enable the virus to establish itself. Temperatures in the lungs are also higher and thus more amenable to the efficient growth of the virus.

The new study involved two different viruses isolated from a single patient -- one from the lungs, the other from the upper respiratory system. The virus from the upper respiratory system exhibited a single amino acid change in one of the key proteins for amplification of influenza virus genes.

The single change identified by the Wisconsin study, says Kawaoka, promotes better virus replication at lower temperatures, such as those found in the upper respiratory system, and in a wider range of cell types.

"This change is needed, but not sufficient," Kawaoka explains. "There are other viral factors needed to cause a viral pandemic" strain of bird flu.

However, Kawaoka and other flu researchers are convinced it is only a matter of time, as more humans and other animals are exposed to the virus, before H5N1 virus takes those steps and evolves into a virus capable of causing a pandemic.

This research is published Oct. 4, 2007 in the journal Public Library of Science Pathogens.

In addition to Kawaoka, authors of the new PLoS Pathogens study include Masato Hatta, Yasuko Hatta, Jin Hyun Kim, Shinji Watanabe of the UW-Madison School of Veterinary Medicine; Kyoko Shinya of Japan's Tottori University; Tung Nguyen of the Vietnamese National Centre for Veterinary Diagnostics; Phuong Song Lien of the Vietnam Veterinary Association; and Quynh Mai Le of the Vietnamese National Institute of Hygiene and Epidemiology.

The work was funded by grants from the U.S. National Institutes of Health and the Japan Science and Technology Agency.

Note: This story has been adapted from material provided by University of Wisconsin-Madison.
 
Re: Bird flu mutating to infect people more easily

A hypothetical question here.....

Various PubMed papers have mentioned an upper "cutoff" temperature of 37-38C for influenza replication at "lower than avian" temperatures, as allowed by the PB2/627 (& possibly others) mutation.

Given the lack of antivirals for a large infected population, could we slow H5N1 replication by lowering the body temperature to below the lower limit of the replication temperature? Would the body's humoral immune system continue to work toward developing antibodies at those temperatures?

If the principle works for birds with a higher body temperature than H5N1 viruses with the PB2/627 changes, why shouldn't it work in the opposite direction?

I began by wondering if people with lower natural body temperatures (mine is usually 97.3 or lower) might be less like to get a severe case of regular flu if the virus replicates more slowly, allowing the immune system to prepare a defense faster than the virus can replicate.

from http://www.virologyj.com/content/3/1/58 .....

Human-tropic influenza viruses are considered to replicate in the upper respiratory tract at 33–37°C, while avian influenza viruses replicate in the gut around 41°C
33C=91.4F, 37C=98.6F, 41C=105.8F

.
 
Last edited:
Back
Top