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Published Date: 2008-05-27 19:00:23
Subject: PRO/AH> Avian influenza H7 - North America: human receptor
Archive Number: 20080527.1728

AVIAN INFLUENZA H7 - NORTH AMERICA: HUMAN RECEPTOR
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******
[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]

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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 naïve animals.

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

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