Bird Flu Genome Study Shows New Strains As new Infections Spread*

The arrows represent the movement of the H5N1 virus into the three
distinct regions represented in the genome study. The green, pink and
yellow arrows depict the three strains of avian flu that have emerged
independently in the West. The orange arrows show the likely source of
all the avian influenza strains, which is in China. From there it has
moved south into Vietnam and west into central Asia and Russia.

by Staff Writers
College Park, MD (SPX) Apr 18, 2007

In a paper in the May issue of Emerging Infectious Diseases, an
international team of researchers report the first ever large-scale
sequencing of western genomes of the deadly avian influenza virus, H5N1.

Their study of 36 genomes of the virus collected from wild birds in
Europe, the Middle East and Africa (EMA), and Vietnam confirms not only
that the virus has very recently spread west from Asia, but that two of
the new western strains have already independently combined, or
"reassorted," to create a new strain.

Several samples also contained the mutation associated with the form of
the "bird flu" that caused several human deaths in 2006. It is the
virus's ability to rapidly mutate into a pathogen that may eventually be
passed between humans that concerns health officials about a worldwide
pandemic of H5N1 influenza.

The study also produced some evidence that strengthens the case that
humans have had an impact on the movement of the flu out of Asia.

"This is the first time anyone's looked at all of the H5N1 genomes in
the west," said Steven Salzberg, the study's lead author and director of
the University of Maryland Center for Bioinformatics and Computational
Biology. "Until now, the studies have been primarily on samples from the
Far East. Our study shows that the virus is spreading west, and that
there have been three separate introductions of H5N1 in Europe, the
Middle East and Africa."

New Strains Confirmed The study's researchers, an unusual team of
scientists from 11 countries that range from U.S. to Iran, collaborated
to share data and sequence H5N1 samples taken from birds in a widely
dispersed geographic region that includes Nigeria, Niger, Sudan, Egypt,
Afghanistan, Iran, Slovenia, Croatia and Italy.

"We found that the EMA strains of the virus are distinct from the
Vietnamese and other Asian strains," said Salzberg, "and that they have
already divided into three separate new strains. One of the new strains
has been the cause of several fatal human cases in Egypt and Iraq."

The research showed that the three new strains, called clades, evolved
independently and in different regions from a single genetic source.
"Our analysis places this source most recently in either Russia or
Quinghai Province in China," Salzberg said.

The study shows that the new Euro-African lineage, which was the cause
of fatal human infections in Egypt and Iraq in 2006, has been introduced
at least three times into the EMA region and has split into three
distinct, independently evolving lineages. Two of those sublineages have
recently reassorted.

The broad dispersal of the different forms of the virus throughout the
different countries over a relatively short period of time points to the
possibility of human movement, rather than wild birds as the reason for
the quick spread of the H5N1.

"The migratory pathways of wild birds don't correspond with the movement
of the genomes that we sequenced," said Salzberg. "Humans carry chickens
between many of the countries in our study, often transporting them
across great distances. That and the weak biosecurity standards in most
rural areas point to human-related movement of live poultry as the
source of the introduction of H5N1 in some countries."

While the study "dramatically increased the number of genomes that have
been sequenced, we have to do more surveys," Salzberg said. "It's
surprising that we found what we did with such a small sample."

International Effort The senior author of the study was Ilaria Capua of
the Istituto Zooprofilattico Sperimentale delle Venezie, Padova, Italy.
Other authors included researchers from Egypt, England, Côte d'Ivoire,
Vietnam, Nigeria, Iran, Afghanistan, Croatia and Slovenia.

"The research team represents an unprecedented collaboration among
authors from many remote laboratories," said Salzberg. "Collaborations
like this one are essential if the scientific community is going to keep
track of avian flu, but most influenza researchers continue to work in
isolation, and to work with a limited and exclusive set of collaborators.

"We have to recognize that the flu knows no boundaries, and we must not
only collaborate widely, but also share our data freely with one
another, as we have in this study."

The flu genomes in this study were all deposited in Genbank, a public
database, immediately after sequencing.

The study was funded by the U.S. National Institute of Allergy and
Infectious Diseases, U.S. National Library of Medicine, U.S. Army
Research Office, the Italian Ministry of Health, the European Commission
for the AVIFLU and FLUAID projects, and the World Organization for
Animal Health and the Food and Agricultural Organization of the United
Nations.

Emerging Infectious Diseases is a journal of the Centers for Disease
Control and Prevention.