PLoS ONE. Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to Human Tracheal Airway Epithelium

[Laidback Al]

Citation: Ayora-Talavera G, Shelton H, Scull MA, Ren J, Jones IM, et al. (2009) Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to HumanTracheal Airway Epithelium. PLoS ONE 4(11): e7836. doi:10.1371/journal.pone.0007836

Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to Human Tracheal Airway Epithelium

Guadalupe Ayora-Talavera, Holly Shelton, Margaret A. Scull, Junyuan Ren, Ian M. Jones, Raymond J. Pickles, Wendy S. Barclay

Abstract
The emergence in 2009 of a swine-origin H1N1 influenza virus as the first pandemic of the 21st Century is a timely reminder
of the international public health impact of influenza viruses, even those associated with mild disease. The widespread
distribution of highly pathogenic H5N1 influenza virus in the avian population has spawned concern that it may give rise to
a human influenza pandemic. The mortality rate associated with occasional human infection by H5N1 virus approximates
60%, suggesting that an H5N1 pandemic would be devastating to global health and economy. To date, the H5N1 virus has
not acquired the propensity to transmit efficiently between humans. The reasons behind this are unclear, especially given
the high mutation rate associated with influenza virus replication. Here we used a panel of recombinant H5 hemagglutinin
(HA) variants to demonstrate the potential for H5 HA to bind human airway epithelium, the predominant target tissue for
influenza virus infection and spread. While parental H5 HA exhibited limited binding to human tracheal epithelium,
introduction of selected mutations converted the binding profile to that of a current human influenza strain HA. Strikingly,
these amino-acid changes required multiple simultaneous mutations in the genomes of naturally occurring H5 isolates.
Moreover, H5 HAs bearing intermediate sequences failed to bind airway tissues and likely represent mutations that are an
evolutionary ‘‘dead end.’’ We conclude that, although genetic changes that adapt H5 to human airways can be
demonstrated, they may not readily arise during natural virus replication. This genetic barrier limits the likelihood that
current H5 viruses will originate a human pandemic.

http://www.plosone.org/article/fetch...esentation=PDF

credits for link to gsgs

 

[JimO]

Re: PLoS ONE. Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to Human Tracheal Airway Epithelium

Is this serious?

 

[Commonground]

Re: PLoS ONE. Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to Human Tracheal Airway Epithelium

Here's an article that is easier to understand.

'Genetic hurdle' halted bird flu
(UKPA) ? 16 hours ago
A genetic hurdle that proved too great may have prevented deadly bird flu causing a terrifying pandemic, researchers have learned.
Scientists discovered the H5N1 strain would have to make at least two simultaneous genetic changes to transmit easily from person-to-person.
The chances of this happening are "extremely low" say the researchers - but they warn that the threat should still be taken seriously.
So far human victims of the H5N1 strain have been confined to people who have been in contact with birds. But when the virus first came to prominence at the turn of the century experts were worried about it causing a devastating pandemic.
When the strain does affect humans, it kills in 60% of cases. Latest figures show the virus has claimed 262 lives so far, with the vast majority of deaths occurring in Asia.
Scientists feared that if the virus mutated into a form that could be transmitted easily between people, many millions might die. Estimates of potential global fatalities ranged from two to 50 million. The new research suggests one reason why the human population has escaped a pandemic is that two mutations would have to occur at the same time to allow it to happen.
At present, the virus can only infect one of the two main types of cell in the mouth and nose, known as a ciliated cell. To transmit between people it would need to infect the other, non-ciliated type of cell as well.
Professor Wendy Barclay, one of the researchers from Imperial College London, said: "H5N1 is a particularly nasty virus, so when humans started to get infected with bird flu, people started to panic.
"An H5N1 pandemic would be devastating for global health. Thankfully, we haven't yet had a major outbreak, and this has led some people to ask, what happened to bird flu? We wanted to know why the virus hasn't been able to jump from human-to-human easily."
"Our new research suggests that it is less likely than we thought that H5N1 will cause a pandemic, because it's far harder for it to infect the right cells."


http://www.google.com/hostednews/ukpress/article/ALeqM5iF_LqFPFM7qCaxvQDcgsgkip2Nbg

 

[JimO]

Re: PLoS ONE. Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to Human Tracheal Airway Epithelium

em Thanks.

 

[Commonground]

Re: PLoS ONE. Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to Human Tracheal Airway Epithelium

I would not have understood the first article either.....em.. -->>

 

[Roehl_JC]

Re: PLoS ONE. Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to Human Tracheal Airway Epithelium

Comment: This earlier research in 2007 indicated that H5N1 COULD still replicate in human upper and lower respiratory tracts. ~jcr
....................
http://www.ncbi.nlm.nih.gov/pubmed/17206149?dopt=AbstractPlus

Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract.
Nicholls JM, Chan MC, Chan WY, Wong HK, Cheung CY, Kwong DL, Wong MP, Chui WH, Poon LL, Tsao SW, Guan Y, Peiris JS.

Department of Pathology, University of Hong Kong, Pok Fu Lam Road, Hong Kong SAR, China. nicholls@pathology.hku.hk

Poor human-to-human transmission of influenza A H5N1 virus has been attributed to the paucity of putative sialic acid alpha2-3 virus receptors in the epithelium of the human upper respiratory tract, and thus to the presumed inability of the virus to replicate efficiently at this site. We now demonstrate that ex vivo cultures of human nasopharyngeal, adenoid and tonsillar tissues can be infected with H5N1 viruses in spite of an apparent lack of these receptors.
PMID: 17206149 [PubMed - indexed for MEDLINE]

 

[Commonground]

Re: PLoS ONE. Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to Human Tracheal Airway Epithelium

This was also published recently....

UW-Madison awarded $9.5 million for influenza research

By Alison Dirr
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Published: Friday, November 20, 2009
Updated: Friday, November 20, 2009



UW-Madison was awarded $9.5 million from the Bill and Melinda Gates Foundation for influenza virus research, it was announced Thursday.

Yoshihiro Kawaoka, UW-Madison professor of virology, is leading the team of international researchers charged with identifying viral mutations. The team hopes to prevent future pandemics by using the information to create an early notification system.
?Early intervention is critical to the control of influenza virus outbreaks,? Kawaoka said in a statement.
The study will focus mainly on avian influenza viruses. Although it is unlikely humans will be affected, one mutation may allow the virus to bond to receptors in human cells. This is when a pandemic usually occurs, the statement said.

?The improved ability to predict whether a virus has pandemic potential would be an invaluable asset to the global community,? Kawaoka said in the statement. ?Millions of lives might be saved if intervention methods?such as social distancing ? vaccine development and production?could be implemented early.?

UW-Madison University Health Services is also taking the prevention path as they prepare for an uptick in H1N1 cases after Thanksgiving and winter breaks, UHS Executive Director Sarah Van Orman said.

Van Orman said UHS will be ready for the next round of outbreaks. UHS plans to offer H1N1 vaccines on a large scale during the first two weeks of December.

According to Van Orman, no flu cases reported have been seasonal flu.


http://www.dailycardinal.com/news/uw-madison-awarded-9-5-million-for-influenza-research-1.938420