Researchers Identify Key Step Bird Flu Virus Takes To Spread Readily In Humans

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.
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.
The study, published today in the journal PLoS Pathogens, details how 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. This adaptation could allow the virus to
infect a wider range of cell types and spread more easily, 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."
There are other yet-to-be-determined changes 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.
As its name implies, bird flu first arises in chickens and other birds.
Humans and other animals in close contact with the birds may become
infected
as 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.


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 that have
the
virus, such as chickens.


According to Kawaoka, the avian virus can reside 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, Kawaoka says,
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.


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.




CITATION: Noda T, Ebihara H, Muramoto Y, Fujii K, Takada A, et al. (2006)
Assembly and budding of Ebolavirus. PLoS Pathog 2(9): e99. DOI:
10.1371/journal.ppat.0020099

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