Evolution of flu strains points to higher risk (H7 and H9)

[Giuseppe]

Re: Evolution of flu strains points to higher risk (H7)

1-4): J Virol. 2007 Jul 25; [Epub ahead of print]

The genesis and evolution of H9N2 influenza viruses in poultry from southern China, 2000 to 2005.

Xu KM, Smith GJ, Bahl J, Duan L, Tai H, Vijaykrishna D, Wang J, Zhang JX, Li KS, Fan XH, Webster RG, Chen H, Peiris JS, Guan Y.
International Institute of Infection and Immunity, Shantou University, Shantou, Guangdong 515031, China; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, Li Ka Sing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China; and Virology Division, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
-

H9N2 influenza viruses have become established in terrestrial poultry in recent two decades in different Asian countries.

Our previous study demonstrated that quail harbor increasing diversity of novel H9N2 reassortants, including both Chicken/Beijing/1/94 (Ck/Bei-like) and Quail/Hong Kong/G1/97 (G1-like) viruses.

However, since 1999 the genesis and evolution of H9N2 viruses in different types of poultry have not been systematically investigated.

In the present study, H9N2 viruses isolated from chicken, duck and other minor poultry were genetically and antigenically characterized.

Our findings demonstrate that Ck/Bei-like H9N2 viruses have been introduced into many different types of poultry including quail, partridge, chukkar, pheasant, Guinea fowl and domestic duck in southern China, while the G1-like viruses were commonly detected from quail, less frequently detected in other minor poultry and not detected in chicken and duck.

Genetic analysis revealed 35 genotypes of H9N2 viruses, including 14 novel genotypes that have not been recognized before.

Our results also suggested that two-way interspecies transmission exist between different types of poultry.

Our study demonstrated that the long-term co-circulation of multiple virus lineages (e.g. H5N1 and H9N2 viruses) in different types of poultry have facilitated these frequent reassortment events that were mostly responsible for current great genetic diversity of H9N2 and H5N1 influenza viruses in this region.

This situation favors the emergence of influenza viruses with pandemic potential.
-
PMID: 17652402 [PubMed - as supplied by publisher]
------

[Giuseppe]

Re: Evolution of flu strains points to higher risk (H7)

(1-4): J Gen Virol. 2007 Jul;88(Pt 7):2035-41.

Antigenic and genetic characterization of H9N2 swine influenza viruses in China.
Cong YL, Pu J, Liu QF, Wang S, Zhang GZ, Zhang XL, Fan WX, Brown EG, Liu JH.
Laboratory of Infectious Diseases, College of Veterinary Medicine, State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing 100094, PR China.
-

As pigs are susceptible to infection with both avian and human influenza A viruses, they have been proposed to be an intermediate host for the generation of pandemic virus through reassortment.

Antigenic and genetic characterization was performed for five swine H9N2 influenza viruses isolated from diseased pigs from different farms.

The haemagglutinin (HA) antigenicity of swine H9N2 viruses was different from that of chicken H9N2 viruses prevalent in northern China.

Genetic analysis revealed that all five isolates had an RLSR motif at the cleavage site of HA, which was different from those of A/duck/Hong Kong/Y280/97 (Dk/HK/Y280/97)-like viruses established in chickens in China.

Phylogenetic analyses indicated that the five swine H9N2 viruses formed novel HA and neuraminidase sublineages that were related closely to those of earlier chicken H9 viruses and were also consistent with the extent of the observed antigenic variation.

The six internal genes of the isolates possessed H5N1-like sequences, indicating that they were reassortants of H9 and H5 viruses.

The present results indicate that avian to porcine interspecies transmission of H9N2 viruses might have resulted in the generation of viruses with novel antigenic and genetic characteristics; therefore, surveillance of swine influenza should be given a high priority.
-
PMID: 17554038 [PubMed - in process]
-----

[gsgs]

Re: Evolution of flu strains points to higher risk (H7)

accessionlengthhostsegmentsubtypecountryyearVirus name23 nucleotide sequencesAgeGender
DQ9974182341Swine1 (PB2)H9N2China2003Influenza A virus (A/swine/Shandong/na/2003(H9N2))
DQ9974272300Swine1 (PB2)H9N2China2003Influenza A virus (A/swine/Shandong/nb/2003(H9N2))
EU5163092341Swine1 (PB2)H9N2China2003Influenza A virus (A/swine/Shandong/w4/2003(H9N2))
DQ981599822Swine1 (PB2)H9N2China2003Influenza A virus(A/swine/Shandong/fHZ/2003(H9N2))
DQ9815752099Swine1 (PB2)H9N2China2003Influenza A virus(A/swine/Shandong/fJN/2003(H9N2))
DQ9816151002Swine1 (PB2)H9N2China2003Influenza A virus(A/swine/Shandong/fLS/2003(H9N2))
DQ9816072207Swine1 (PB2)H9N2China2003Influenza A virus(A/swine/Shandong/fNY/2003(H9N2))
DQ9816231115Swine1 (PB2)H9N2China2003Influenza A virus(A/swine/Shandong/fZC/2003(H9N2))
EU5163172341Swine1 (PB2)H9N2China2004Influenza A virus (A/swine/Guangdong/wxl/2004(H9N2))
EU5028982341Swine1 (PB2)H9N2China2004Influenza A virus (A/swine/Jiangxi/1/2004(H9N2))
EU5029062341Swine1 (PB2)H9N2China2004Influenza A virus (A/swine/Jiangxi/wx2/2004(H9N2))
DQ981583846Swine1 (PB2)H9N2China2004Influenza A virus(A/swine/Henan/2/2004(H9N2))
DQ9815352040Swine1 (PB2)H9N2China2004Influenza A virus(A/swine/Henan/3/2004(H9N2))
DQ981543831Swine1 (PB2)H9N2China2004Influenza A virus(A/swine/Henan/4/2004(H9N2))
DQ9815592034Swine1 (PB2)H9N2China2004Influenza A virus(A/swine/Henan/5/2004(H9N2))
DQ981591848Swine1 (PB2)H9N2China2004Influenza A virus(A/swine/Henan/6/2004(H9N2))
DQ981551860Swine1 (PB2)H9N2China2004Influenza A virus(A/swine/Henan/7/2004(H9N2))
DQ9815672084Swine1 (PB2)H9N2China2004Influenza A virus(A/swine/Henan/8/2004(H9N2))
EF6127492341Swine1 (PB2)H9N2China2005Influenza A virus (A/swine/Guangxi/58/2005(H9N2))
EU0863162341Swine1 (PB2)H9N2China2005Influenza A virus (A/swine/Guangxi/FS2/2005(H9N2))
EU0863322341Swine1 (PB2)H9N2China2005Influenza A virus (A/swine/Guangxi/S11/2005(H9N2))
EU0863332341Swine1 (PB2)H9N2China2005Influenza A virus (A/swine/Guangxi/S15/2005(H9N2))
DQ9974351164Swine1 (PB2)H9N2China2005Influenza A virus (A/swine/Shandong/nc/2005(H9N2))




differences in the 8 segments in 0/00

A/swine/Shandong/fNY/2003(H9N2)
A/swine/Shandong/2/03(H5N1) 
 4, 18,  7,403,  5,467, 17,  0

and in segment 2 (PB1) : {and Henan - segment 5}

 18 >A/swine/Guangxi/S11/2005(H9N2)
 19 >A/swine/Guangxi/58/2005(H9N2) 
 20 >A/swine/Guangxi/S15/2005(H9N2)

 23 >A/swine/Guangxi/wz/2004(H5N1)    18: 69, 38, 94,394, 86,443, 71, 97, - 19: 62, 39, 94,395, 86,445, 66, 97, - 20:113, 37, 94,394, 84,445, 66, 99
 24 >A/swine/Henan/wy/2004(H5N1)      18: 64, 20, 94,395, 23,446, 90,100, - 19: 47, 20, 94,396, 23,447, 85,100, - 20:105, 20, 94,395, 21,447, 85,102
 25 >A/swine/Anhui/ca/2004(H5N1)      18: 67, 23, 96,398, 91,453, 92,102, - 19: 52, 23, 96,399, 90,455, 87,102, - 20:108, 23, 96,398, 88,455, 87,105
 26 >A/swine/Fujian/1/2003(H5N1)      18: 84, 23, 95,397, 68,444, 86, 96, - 19: 78, 23, 95,398, 68,445, 81, 96, - 20:120, 22, 94,397, 67,445, 81, 98
 27 >A/swine/Fujian/F1/2001(H5N1)     18: 83, 25, 96,393, 68,446, 83, 94, - 19: 78, 25, 96,395, 68,447, 78, 94, - 20:120, 24, 95,393, 67,447, 78, 97

[Giuseppe]

Re: Evolution of flu strains points to higher risk (H7 and H9)

Contemporary North American influenza H7 viruses possess human receptor specificity: Implications for virus transmissibility

Jessica A. Belser*,, Ola Blixt, Li-Mei Chen*, Claudia Pappas*, Taronna R. Maines*, Neal Van Hoeven*, Ruben Donis*, Julia Busch, Ryan McBride, James C. Paulson, Jacqueline M. Katz*, and Terrence M. Tumpey*,

*Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333; Emory University, Atlanta, GA 30322; and Departments of Physiological Chemistry and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037

Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved March 21, 2008 (received for review February 7, 2008)

Avian H7 influenza viruses from both the Eurasian and North American lineage have caused outbreaks in poultry since 2002, with confirmed human infection occurring during outbreaks in The Netherlands, British Columbia, and the United Kingdom.

The majority of H7 infections have resulted in self-limiting conjunctivitis, whereas probable human-to-human transmission has been rare.

Here, we used glycan microarray technology to determine the receptor-binding preference of Eurasian and North American lineage H7 influenza viruses and their transmissibility in the ferret model.

We found that highly pathogenic H7N7 viruses from The Netherlands in 2003 maintained the classic avian-binding preference for 2?3-linked sialic acids (SA) and are not readily transmissible in ferrets, as observed previously for highly pathogenic H5N1 viruses.

However, H7N3 viruses isolated from Canada in 2004 and H7N2 viruses from the northeastern United States isolated in 2002?2003 possessed an HA with increased affinity toward 2?6-linked SA, the linkage type found prominently on human tracheal epithelial cells.

We identified a low pathogenic H7N2 virus isolated from a man in New York in 2003, A/NY/107/03, which replicated efficiently in the upper respiratory tract of ferrets and was capable of transmission in this species by direct contact.

These results indicate that H7 influenza viruses from the North American lineage have acquired sialic acid-binding properties that more closely resemble those of human influenza viruses and have the potential to spread to na?ve animals.
-

http://www.pnas.org/cgi/content/short/105/21/7558?rss=1

------

[Sally Furniss]

Re: Evolution of flu strains points to higher risk (H7 and H9)

Mild American Bird-Flu Strains Gained Ability to Attack Humans
By John Lauerman
<!-- WARNING: #foreach: $wnstory.ATTS: null at /bb/data/web/templates/webmacro_en/washingtonstory.wm:266.2 --> <!-- WARNING: #foreach: $wnstory.ATTS: null at /bb/data/web/templates/webmacro_en/washingtonstory.wm:280.19 --> May 26 (Bloomberg) -- Mild bird flu strains circulating in North America have gained some ability to infect human cells, and should be monitored for dangerous mutations, government researchers said.
The virus family, called H7, is genetically different than the H5N1 strain that has killed millions of birds and hundreds of people, said Terrence Tumpey, a U.S. Centers for Disease Control and Prevention scientist in Atlanta. More mutations in the H7 strain could make it dangerous to humans, he said.
People don't have natural immunity to many strains of flu spreading in birds, allowing these viruses to cause severe infections when they enter human cells. Some strains of H7 have increased their ability to stick to proteins on the surface of human lung cells, a key step in infection that may at some point allow its spread from one human to another, Tumpey said in a study in the Proceedings of the National Academy of Sciences journal.
``This underscores the importance of continued surveillance so we can be best prepared for early response to a pandemic threat,'' he said in a telephone interview.
At least 241 people have died of H5N1 bird flu since 2003, most of them in Asia. A worldwide network of laboratories collects and analyzes samples for mutations that might allow the virus to spread quickly from person to person.
Tumpey analyzed H7 viruses that infected poultry and people from 2002 through 2004. One was an H7 strain that caused an outbreak in the Netherlands in 2003, infecting about 80 people and killing one person.
Eye Infections
That strain wasn't well adapted to human lung cells, and most human infections were in the eye, Tumpey said. His analysis showed the virus prefers attaching to a molecule in birds' intestines, called alpha 2-3.
Other H7 strains circulating at the same time in Canada and the U.S., however, had the ability to attach to a cell surface molecule called alpha 2-6. That molecule is found in the breathing tissues of humans and animals, and is a common target for seasonal flu viruses that cause annual outbreaks and spread quickly through the population, he said.
One H7 strain that infected a New York man in 2004 was easily transmitted among ferrets, the study showed. Ferrets and humans are susceptible to many of the same flu viruses.
While the finding is important, other characteristics probably contribute to the ability of viruses to spread and make people ill, said Albert Osterhaus, a virologist at the Erasmus Medical Center in Rotterdam. Other factors, such as whether the virus grows in the human nose and throat, rather than deep in the lungs, may allow it to spread quickly, he said.
Respiratory Tract
``Those that replicate in the upper respiratory tract are more likely to be transmitted between mammals,'' he said in a telephone interview. The ability to bind to human cells ``is not the whole story.''
While these H7 viruses are ``low pathogenic,'' meaning they rarely cause deaths, they nonetheless pose a threat, Tumpey said.
``We have to be aware of these viruses just like we're aware of H5 viruses,'' he said. ``They have the potential to mutate to high pathogenic and they are in our backyard.''
Three influenza pandemics occurred last century in 1918, 1957 and 1968. The most lethal by far was the 1918 ``Spanish flu'' that killed as many as 50 million people worldwide.
To contact the reporter on this story: John Lauerman in Boston at jlauerman@bloomberg.net .
Last Updated: May 26, 2008 17:00 EDT

http://www.bloomberg.com/apps/news?pid=washingtonstory&sid=aVWZxrgJpeo0

[HenryN]

Re: Evolution of flu strains points to higher risk (H7 and H9)

Contemporary North American influenza H7 viruses possess human receptor specificity: Implications for virus transmissibility

Jessica A. Belser*,, Ola Blixt, Li-Mei Chen*, Claudia Pappas*, Taronna R. Maines*, Neal Van Hoeven*, Ruben Donis*, Julia Busch, Ryan McBride, James C. Paulson, Jacqueline M. Katz*, and Terrence M. Tumpey*,

*Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333; Emory University, Atlanta, GA 30322; and Departments of Physiological Chemistry and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037

Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved March 21, 2008 (received for review February 7, 2008)

Avian H7 influenza viruses from both the Eurasian and North American lineage have caused outbreaks in poultry since 2002, with confirmed human infection occurring during outbreaks in The Netherlands, British Columbia, and the United Kingdom.

The majority of H7 infections have resulted in self-limiting conjunctivitis, whereas probable human-to-human transmission has been rare.

Here, we used glycan microarray technology to determine the receptor-binding preference of Eurasian and North American lineage H7 influenza viruses and their transmissibility in the ferret model.

We found that highly pathogenic H7N7 viruses from The Netherlands in 2003 maintained the classic avian-binding preference for 2?3-linked sialic acids (SA) and are not readily transmissible in ferrets, as observed previously for highly pathogenic H5N1 viruses.

However, H7N3 viruses isolated from Canada in 2004 and H7N2 viruses from the northeastern United States isolated in 2002?2003 possessed an HA with increased affinity toward 2?6-linked SA, the linkage type found prominently on human tracheal epithelial cells.

We identified a low pathogenic H7N2 virus isolated from a man in New York in 2003, A/NY/107/03, which replicated efficiently in the upper respiratory tract of ferrets and was capable of transmission in this species by direct contact.

These results indicate that H7 influenza viruses from the North American lineage have acquired sialic acid-binding properties that more closely resemble those of human influenza viruses and have the potential to spread to na?ve animals.
-

http://www.pnas.org/cgi/content/short/105/21/7558?rss=1

------

Earlier commentary

http://www.recombinomics.com/News/04290801/H7N2_NY_Reassortant_Ferrets.html

[HenryN]

Re: Evolution of flu strains points to higher risk (H7 and H9)

Earlier discussion - Title of thread: Human H7N2 in New York

http://www.flutrackers.com/forum/showthread.php?t=66348

[HenryN]

Re: Evolution of flu strains points to higher risk (H7 and H9)

CDC has pulled sequences

http://www.flutrackers.com/forum/showpost.php?p=152098&postcount=1

[sharon sanders]

Re: Evolution of flu strains points to higher risk (H7 and H9)

CDC has pulled sequences

http://www.flutrackers.com/forum/sho...98&postcount=1

So, do we have the only publicly available set of these sequences?

[HenryN]

Re: Evolution of flu strains points to higher risk (H7 and H9)

So, do we have the only publicly available set of these sequences?

I am looking for replacement sequences, but haven't found them yet. The links still work for the sequences, but finding the sequences without the links is a challenge because they are not in the main database.

[rymich13]

Re: Evolution of flu strains points to higher risk (H7 and H9)

This just goes to show that any avian flu has the potential to become pandemic.

[HenryN]

Evolution of flu strains points to higher risk (H7 and H9)

http://www.recombinomics.com/News/04280802/H7N2_NY_Reassortant.html

http://www.recombinomics.com/News/04280803/H7N2_NY_Reassortant_Concerns.html

http://www.recombinomics.com/News/04290801/H7N2_NY_Reassortant_Ferrets.html

[HenryN]

Re: Evolution of flu strains points to higher risk (H7 and H9)

AVIAN INFLUENZA H7 - NORTH AMERICA: HUMAN RECEPTOR
**************************************************
A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>

******
[1]
Date: Mon 26 May 2008
Source: Bloomberg.com [edited]
<http://www.bloomberg.com/apps/news?pid=20601082&sid=aVWZxrgJpeo0&refer=canada>


Mild American Bird-Flu Strains Gained Ability to Attack Humans
--------------------------------------------------------------
Mild bird flu strains circulating in North
America have gained some ability to infect human
cells, and should be monitored for dangerous
mutations, government researchers said. The virus
family [i.e., the influenza virus serotype -
Mod.CP], called H7, is genetically different than
the H5N1 strain that has killed millions of birds
and hundreds of people, said Terrence Tumpey, a
U.S. Centers for Disease Control and Prevention
(CDC) scientist in Atlanta. More mutations in the
H7 strain could make it dangerous to humans, he
said. People don't have natural immunity [i.e.,
innate resistance] to many strains of flu
spreading in birds, allowing these viruses to
cause severe infections when they enter human
cells. Some strains of H7 have increased their
ability to stick to proteins on the surface of
human lung cells, a key step in infection that
may at some point allow its spread from one human
to another, Tumpey said in a study in the
Proceedings of the National Academy of Sciences
journal. "This underscores the importance of
continued surveillance so we can be best prepared
for early response to a pandemic threat," he said
in a telephone interview.

At least 241 people have died of H5N1 bird flu
since 2003, most of them in Asia. A worldwide
network of laboratories collects and analyzes
samples for mutations that might allow the virus
to spread quickly from person to person. Tumpey
analyzed H7 viruses that infected poultry and
people from 2002 through 2004. One was an H7
strain that caused an outbreak in the Netherlands
in 2003, infecting about 80 people and killing
one person. That strain wasn't well adapted to
human lung cells, and most human infections were
in the eye, Tumpey said. His analysis showed the
virus prefers attaching to a molecule in birds'
intestines, called alpha 2-3[-linked sialic
acid]. Other H7 strains circulating at the same
time in Canada and the U.S., however, had the
ability to attach to a cell surface molecule
called alpha 2-6[-linked sialic acid]. That
molecule is found in the breathing tissues of
humans and animals, and is a common target for
seasonal flu viruses that cause annual outbreaks
and spread quickly through the population, he
said.

One H7 strain that infected a New York man in
2004 was easily transmitted among ferrets, the
study showed. Ferrets and humans are susceptible
to many of the same flu viruses. While the
finding is important, other characteristics
probably contribute to the ability of viruses to
spread and make people ill, said Albert
Osterhaus, a virologist at the Erasmus Medical
Center in Rotterdam. Other factors, such as
whether the virus grows in the human nose and
throat, rather than deep in the lungs, may allow
it to spread quickly, he said. "Those that
replicate in the upper respiratory tract are more
likely to be transmitted between mammals," he
said in a telephone interview. The ability to
bind to human cells "is not the whole story."

While these H7 viruses are "low pathogenic,"
meaning they rarely cause deaths [in birds], they
nonetheless pose a threat, Tumpey said. "We have
to be aware of these viruses just like we're
aware of H5 viruses," he said. "They have the
potential to mutate to high pathogenic and they
are in our backyard."

A total of 3 influenza pandemics occurred last
century in 1918, 1957 and 1968. The most lethal
by far was the 1918 "Spanish flu" that killed as
many as 50 million people worldwide.

[Byline: John Lauerman]

--
Communicated by:
ProMED-mail
<promed@promedmail.org>

******
[2]
Date: Mon 26 May 2008
Source: The Times online [edited]
<http://www.timesonline.co.uk/tol/news/uk/science/article4009755.ece>


Scientists identify 2nd H7 strain of bird flu that could cause pandemic
-----------------------------------------------------------------------
The H5N1 strain of bird flu that has killed 241
people is not the only one that could trigger a
pandemic, according to research in America. A few
H7 strains of the flu virus have started to
evolve some of the traits they would need to
infect people easily, scientists have discovered.
The findings, from a team led by Terrence Tumpey,
of the US Centers for Disease Control and
Prevention (CDC) in Atlanta, show that while
there is no immediate indication that H7 flu is
about to acquire potentially damaging mutations,
it is critical that global surveillance and
research covers this virus class [i.e., influenza
virus serotype] as well as the more obvious H5N1,
scientists said.

The H5N1 strain has been regarded as the most
deadly strain since it appeared in Asia in 2003.
Although it has a death rate of more than 60
percent, it has not yet acquired the ability to
move from person to person, which would be a
prerequisite for a pandemic. There has been only
one case in which it is considered probable that
the virus was transmitted from person to person,
and analysis of the virus's genetic structure has
not yet revealed mutations that would allow it to
infect people more easily. It is generally caught
from close contact with infected birds, in which
it is endemic [enzootic] in some parts of the
world, particularly in Asia.

The H7 influenza viruses also primarily affect
birds. A deadly version of the H7N7 strain hit
poultry in the Netherlands in 2003, and a less
severe form, H7N2, broke out in the UK last year
[2007]. Between 2002 and 2004 several outbreaks
of H7N3 and H7N2 have been reported. In each of
these incidents a few human cases of infection
have been reported. One vet died during the Dutch
outbreak and about 80 people suffered
conjunctivitis, an eye infection that is not
life-threatening. The UK outbreak also led to
cases of conjunctivitis and a few mild
respiratory infections.

Dr. Tumpey's analysis of a 2003 case in New York
has shown, however, that the H7N2 virus
responsible is capable of replicating in the
respiratory tract of mammals. This quality is
unusual among avian viruses, and indicates that
it could possibly be transmissible from person to
person. A study with ferrets -- a standard animal
model of flu in humans -- also revealed that this
H7N2 strain could be passed from animal to
animal. This suggests that the virus could be
acquiring an ability to bind to sugars found on
the cells of the human windpipe. This happened
during all 3 of the 20th-century flu pandemics,
which occurred in 1918, 1957 and 1968. "These
findings suggest that the H7 viruses are
partially adapted to recognise the receptors that
are preferred by the human influenza virus," Dr.
Tumpey said. "The finding ... underscores the
necessity for continued surveillance and study of
these viruses as they continue to resemble
viruses with pandemic potential."

Each of the 3 flu pandemics of the last century
was caused by a humanised strain of flu. The
Spanish Flu of 1918-19, which killed up to 40
million people, was caused by an H1N1 virus. The
1957-58 Asian Flu was caused by an H2N2 strain,
and the 1968-69 Hong Kong Flu by an H3N2 strain.

[Byline: Mark Henderson]

--
Communicated by:
ProMED-mail
<promed@promedmail.org>

******
[3]
Date: Mon 26 May 2008
Source: The Canadian Press [edited]
<http://canadianpress.google.com/article/ALeqM5gNcxp7Ae1ILxfVkoRKTL-RTKeCGg>


North American bird flu viruses becoming more adapted to humans
---------------------------------------------------------------
North American avian flu viruses of the H7
subtype -- like the H7N3 viruses responsible for
British Columbia's massive poultry outbreak in
2004 -- seem to have adapted to more easily
invade the human respiratory tract, a new
American study suggests. The adaptation is still
only partial and the findings do not suggest the
viruses are imminently poised to trigger a
pandemic. But experts say they underscore the
fact that H7 flu viruses need to be watched and
studied.

"I think this is certainly amongst the most
dangerous (avian flu) viruses out there," said
virologist Dr. Ron Fouchier, with the Erasmus
Medical Centre in Rotterdam, the Netherlands.
"And I think we need to continue to develop
vaccines for H7 just as well as H5(N1)." Fouchier
was commenting on a scientific paper published
Monday by the journal Proceedings of the National
Academy of Sciences. Fouchier's research on avian
influenza includes study of the H7N7 outbreak in
the Netherlands in 2003, but he was not involved
in this work.

Scientists from the U.S. Centers for Disease
Control (CDC) reported on their research on a
number of H7 viruses, looking both at the types
of receptor cells -- bird or human -- each was
more inclined to latch onto and whether the
viruses transmitted from infected to uninfected
ferrets. Of all available animal models,
influenza infection in ferrets is considered to
mirror most closely the course the disease takes
in humans.

Human flu viruses that circulate every winter
have adapted to be able to bind to the receptors
that predominate in the human respiratory tract,
known as alpha 2-6 receptors. Avian viruses, on
the other hand, prefer the alpha 2-3 receptors
found in the guts of wild birds (their natural
host) and domestic poultry. Those receptors are
scarce in the human upper respiratory tract. It
is assumed that an avian virus would need to make
this kind of adaptation -- learning to latch onto
the human-type receptors -- before it could
transmit easily to and among humans.

Among the H7 viruses the CDC scientists studied
were H7N3 viruses recovered from the two British
Columbians infected during an outbreak in the
poultry farm-dense Fraser Valley in 2004. More
than 17 million chickens were destroyed in the
efforts to stop that outbreak. Also tested was a
virus recovered from a strange H7N2 infection in
the Yonkers area of New York City. A man who had
no known contact with poultry was hospitalized in
November 2003. Because he was suffering from
other ailments, the fact that he was also
harbouring an avian flu virus was not detected at
the time. In fact, it was thought he had human
flu. Several months later testing at the CDC
revealed the rare infection. How the man caught
the virus remains a mystery. Of all the H7
viruses studied for this work, the New York man's
seemed most adapted to humans. It bound more
easily to the receptors found in the lining of
the human upper respiratory tract and had
decreased binding to bird receptor cells. And
when ferrets were inoculated with the virus, it
spread from the infected animals to healthy
animals placed in the same cages.

But in general H7 viruses from North America that
have been isolated from about 2002 onwards seem
to have developed an increasing affinity for the
human-type receptors, said Dr. Terrence Tumpey,
the CDC scientist who led the work. "These
viruses are partially adapted to recognize the
receptors preferred by human influenza viruses,
but not completely," he said in an interview from
Atlanta. "It needs to be adapted further. But I
think it shows that potentially that these
viruses are changing. Because we can look at an
older North American H7 or Eurasian H7s or H5s
and they have the characteristic avian influenza
binding properties. Whereas these seem to be
different and possibly changing."

At this point it is unclear what additional
changes would be needed for an H7 virus to fully
adapt to a human host -- or whether H7 viruses
could acquire all those changes. When H7 viruses
have caused human cases, the ensuing disease has
typically been mild, with people suffering
conjunctivitis (pink eye) and-or mild respiratory
symptoms. There is one exception -- a
veterinarian infected with an H7N7 virus died
during the Dutch outbreak.

The mildness of the disease may have lulled some
people into a sense of complacency about H7
viruses, said Dr. Danuta Skowronski, an influenza
expert at the British Columbia Centre for Disease
Control. But she insisted the fact that H7
viruses don't induce the life-threatening disease
seen in H5N1 infection doesn't mean they
shouldn't be viewed as a serious pandemic threat.
"H7, with its mildness, may be more -- I hate to
anthropomorphize -- but more devious. Because
through surreptitious spread -- because it's
milder, it's unrecognized, people might dismiss
it more -- it may actually have more opportunity
to adapt to the human respiratory tract," she
said from Vancouver. "And even though it may be
mild today, even though it may not transmit
easily today, the potential is always there for
it to change. And basically we don't want new
(flu) subtypes in the human population. We've got
enough to deal with the humanized strains.

--
Communicated by:
ProMED-mail Rapporteur Mary Marshall

[The above three reports describe with increasing
clarity and scientific accuracy the outcome of a
study of the human receptor specificities of
subtype H7 avian influenza viruses which have
been isolated in North America up to 2004. These
results indicate that H7 influenza viruses from
the North American lineage have acquired sialic
acid-binding properties that more closely
resemble those of human influenza viruses and
have the potential to spread to naive animals
(ferrets in these experiments). While these
findings are important, other characteristics
probably contribute to the ability of viruses to
spread and cause illness in the human population.
Nevertheless these findings clearly demonstrate
the necessity for increased surveillance and
further study of these viruses as they continue
to resemble viruses with pandemic potential.
However, it should not be concluded that an H7
pandemic is imminent since similar viruses have
probably continued to circulate since 2004.

The Abstract of Open Access paper published in
the 27 May 2008 issue of the Proceedings of the
National Academy of Sciences USA, vol. 105, no.
21, 7557563, 1908
(<http://www.pnas.org/cgi/content/abstract/105/21/7558>) is reproduced below.

Title: Contemporary North American influenza H7
viruses possess human receptor specificity:
Implications for virus transmissibility

Authors: Jessica A. Belser*,**, Ola Blixt***,
Li-Mei Chen*, Claudia Pappas*, Taronna R.
Maines*, Neal Van Hoeven*, Ruben Donis*, Julia
Busch***, Ryan McBride***, James C. Paulson***,
Jacqueline M. Katz*, and Terrence M. Tumpey*

At: *Influenza Division, National Center for
Immunization and Respiratory Diseases, Centers
for Disease Control and Prevention, Atlanta, GA
30333;
**Emory University, Atlanta, GA 30322; and
***Departments of Physiological Chemistry and
Molecular Biology, The Scripps Research
Institute, La Jolla, CA 92037

Abstract: Avian H7 influenza viruses from both
the Eurasian and North American lineage have
caused outbreaks in poultry since 2002, with
confirmed human infection occurring during
outbreaks in The Netherlands, British Columbia,
and the United Kingdom. The majority of H7
infections have resulted in self-limiting
conjunctivitis, whereas probable human-to-human
transmission has been rare. Here, we used glycan
microarray technology to determine the
receptor-binding preference of Eurasian and North
American lineage H7 influenza viruses and their
transmissibility in the ferret model. We found
that highly pathogenic H7N7 viruses from The
Netherlands in 2003 maintained the classic
avian-binding preference for 2-3-linked sialic
acids (SA) and are not readily transmissible in
ferrets, as observed previously for highly
pathogenic H5N1 viruses. However, H7N3 viruses
isolated from Canada in 2004 and H7N2 viruses
from the northeastern United States isolated in
2002-2003 possessed an HA with increased affinity
toward 2-6-linked SA, the linkage type found
prominently on human tracheal epithelial cells.
We identified a low pathogenic H7N2 virus
isolated from a man in New York in 2003,
A/NY/107/03, which replicated efficiently in the
upper respiratory tract of ferrets and was
capable of transmission in this species by direct
contact. These results indicate that H7 influenza
viruses from the North American lineage have
acquired sialic acid-binding properties that more
closely resemble those of human influenza viruses
and have the potential to spread to na?ve animals.

There are 48 references to avian H7 influenza
viruses in the ProMED-mail archive. Those since
2004 are listed below. - Mod.CP]

[see also:
Avian influenza (66): Japan, swan, Denmark, LPH7, OIE 20080430.1484
Avian influenza (65): Japan, swan, Denmark, LPAI, H7 20080429.1479
Avian influenza (27): Bulgaria, wild duck, H7, OIE 20080203.0437
Avian influenza (25) - Bulgaria, wild duck, H7 20080202.0415
2007
----
Avian influenza (177): S. Korea, LPAI H7, susp. 20071124.3797
Avian influenza, poultry vs migratory birds (35): H7 20070902.288
2006
----
Avian influenza (170) - Netherlands, LPAI H7 20060805.2160
Avian influenza (168) - Netherlands, LPAI H7 20060801.2126
Avian influenza - worldwide (99): UK H7, Germany 20060427.1226
Avian influenza, H7, poultry - Lebanon: RFI 20060402.0988
2005
----
Avian influenza, H7 - North Korea (07) 20050707.1927
Avian influenza, H7 - North Korea (06) 20050425.1152
Avian influenza, H7 - North Korea (05): regional cooperation 20050422.1126
Avian influenza, H7 - North Korea (04): EU import restrict. 20050415.1084
Avian influenza, H7 - North Korea (03) 20050409.1027
Avian influenza, H7 - North Korea (02): OIE 20050408.1016
Avian influenza, H7 - North Korea 20050405.0978]
....................cp/ejp/lm

[Malcolm]

Re: Evolution of flu strains points to higher risk (H7 and H9)

MAY 2007:

Wales UK H7N2 confirmed outbreak is missing from above Promed references:

06-JUN-07 PRO/AH/EDR> Avian influenza H7N2, human - UK (Wales) (08) 20070606.1830
04-JUN-07 PRO/AH/EDR> Avian influenza H7N2, human - UK (Wales) (07): WHO 20070604.1810
03-JUN-07 PRO/AH/EDR> Avian influenza (95): UK (Wales), LPAI H7N2, 2nd location, NOT 20070603.1794
01-JUN-07 PRO/AH/EDR> Avian influenza H7N2, human - UK (Wales) (06) 20070601.1772
29-MAY-07 PRO/AH/EDR> Avian influenza H7N2, human - UK (Wales) (05), WHO 20070529.1734
28-MAY-07 PRO/AH/EDR> Avian influenza H7N2, human - UK (Wales)(04) 20070528.1714
27-MAY-07 PRO/AH> Avian influenza (90) - UK (Wales): LPAI H7N2, epid. control 20070527.1709
PRO/AH/EDR> Avian influenza H7N2, human - UK (Wales)(03) 20070527.1702
26-MAY-07 PRO/AH/EDR> Avian influenza (89) - UK (Wales): LPAI H7N2, 2nd location, susp. 20070526.1692
PRO/AH/EDR> Avian influenza H7N2, human - UK (Wales) (02) 20070526.1682
PRO/AH/EDR> Avian influenza (88) - UK (Wales): LPAI H7N2 20070526.1681
25-MAY-07 PRO/AH/EDR> Avian influenza H7N2, human - UK (Wales) 20070525.1674
24-MAY-07 PRO/AH/EDR> Avian influenza (86) - UK (Wales): LPAI H7N2 20070524.1661

http://news.bbc.co.uk/1/hi/wales/6699595.stm

Last Updated: Tuesday, 29 May 2007, 07:21 GMT 08:21 UK

Avian flu contacts 'identified'


Teachers and pupils at Ysgol Henllan have been given treatment
Health officials say they have identified all the people who came into close contact with an outbreak of avian flu at a smallholding in north Wales.

The number of people found to have had contact with the disease rose over the weekend to 142, of which 12 are being treated as being positive for bird flu.

The mild H7N2 strain of bird flu was first found last week among chickens at a farm near Corwen, Conwy.

Children at a Denbighshire school are being offered anti-viral medication.

A year five pupil at Ysgol Henllan suspected of contracting the virus has been linked to the smallholding.

A dozen children aged nine and 10 and two teachers at the school are being given tamiflu treatments as a precaution.

School meeting

The National Public Health Service of Wales has said a total of 142 people have had either direct or indirect contact with the virus, which is not the virulent H5N1 strain of avian flu.

Twelve people are being treated as "positive", but no-one is seriously ill.

Of the 142 to come into contact with the virus, 47 came into contact "in the household setting," 14 in the school and 81 in "the workplace setting".

Health officials held a meeting for concerned parents at the school on Monday evening, in which it was stressed the risk of anyone contracting the virus is very small.

Conwy smallholding where bird flu has been confirmed
An outbreak was first confirmed at a smallholding in Conwy

Another meeting for those who could not attend is planned for Tuesday evening.

The National Public Health Service of Wales's director for north Wales, Andrew Jones, said it was "reassuring" so few people had reported symptoms.

He said: "We are treating 12 cases as positive.

"We always approach schools in a precautionary way.

"We are advising them that the risk to the population is low and that avian flu is a disease of birds.

"It would be very unusual for it to spread from person to person."

Hugh Pennington, a microbiologist and bird flu expert from Aberdeen University, added: "You have to be in quite close contact with infected birds to get infected.

"It doesn't spread from one infected person to another.

"It's still a bird virus - someone infected isn't going to cause any more human cases."

John Lloyd, who has two children at Ysgol Henllan, said he was satisfied the outbreak has been handled well by officials after attending a meeting with parents on Monday.

He said: "They felt it was all under control which confirmed what I felt to be honest.

"I think they've done enough to keep the public calm."

Birds slaughtered

The first confirmed case involved a smallholding at Llanfihangel Glyn Myfyr, Conwy.

Owners Tony Williams and Barbara Cowling, who have tested negative for the virus, called in a vet after their Rhode Island Red chickens began to die.

They bought the chickens at Chelford Market at Macclesfield, Cheshire, some 70 miles (112 km) away, on 7 May.

A total of 30 chickens from the smallholding have now been slaughtered after 15 birds died.

Officials have stressed that the disease found at the Conwy farm was the H7N2 strain of bird flu, not the more virulent H5N1.

The second possible case emerged on Saturday about 35 miles (56 km) away, at a farm on the outskirts of Efailnewydd, near Pwllheli. It has also been linked to the market.

[Gert van der Hoek]

Re: Evolution of flu strains points to higher risk (H7 and H9)

Do not know if this is usefull, this is some additional information (sequences?) on the PNAS article:

http://www.pnas.org/cgi/data/0801259105/DCSupplemental/Supplemental_PDF

Full text of the PNAS article here:

http://www.pnas.org/cgi/content/full/105/21/7558

..