Scientists Find Mutations That Let Bird Flu Adapt To HumansMain
Category: Bird Flu / Avian Flu News
Article Date: 21 Nov 2006 - 1:00am (PST)
By comparing influenza viruses found in birds with those of the
avian virus that have also infected human hosts, researchers have
identified key genetic changes required for pandemic strains of
bird flu.
The new work, reported in the Nov. 16 issue of the journal Nature,
illustrates the genetic changes required for the H5N1 avian
influenza virus to adapt to easily recognize the receptors that are
the gateway to human cells.
"We identified two changes that are important," says Yoshihiro
Kawaoka, the senior author of the Nature paper and a virologist at
the University of Wisconsin-Madison School of Veterinary Medicine.
"Both changes are needed for the H5N1 virus to recognize human
receptors."
The new report provides a molecular blueprint for the genetic
changes required to transform a virus that only infects birds to a
virus capable of easily recognizing human receptors. Receptors are
molecules on the surface of cells that permit the virus to dock
with the cell and commandeer it to initiate a cascade of infection.
By knowing what genetic changes are required for the virus to
easily infect human cells, it may be possible to detect the
emergence of pandemic strains earlier, providing public health
officials and vaccine manufacturers with precious time to prepare
for a global outbreak of highly pathogenic influenza. To be
successful, a virus must be able to recognize and attach to a host
cell. But human and avian influenza viruses recognize different
cell receptors. Avian flu viruses have demonstrated an ability to
evolve to easily infect humans by exchanging genes with human
viruses that subsequently permit them to recognize human receptor
molecules and gain easy access to cells, typically in the human
respiratory system.
The change is thought to occur when human patients are exposed at
the same time to a human flu virus and an avian flu virus. Most
viruses, including influenza, readily swap genes with one
another.
In the new study, conducted by an international team of
researchers, the viruses isolated from human patients in Vietnam
and Thailand could recognize both human and avian cell receptors.
By contrast, the viruses found in chickens and ducks could only
recognize the receptors on avian cells.
The work helps flesh out the changes that have occurred in the
worrisome strain of avian influenza virus known as H5N1, a strain
some fear could be the organism that will trigger a pandemic of
virulent human influenza. The avian virus has already changed
dramatically from when it was first identified in 1997, says
Kawaoka, who also holds an appointment at the University of
Tokyo.
"There are big differences between the virus first found in 1997
and the virus we see now," Kawaoka explains. "We are watching this
virus turn itself into a human pathogen."
The mutations found by Kawaoka's group have not yet conferred a
complete ability on avian flu to easily recognize the topography of
human cells, but they are key steps on that pathway. More
mutations, says Kawaoka, will be required for the virus to fully
adapt to humans, but it is not known how many mutations are needed
for such a change.
However, if scientists are able to continue to monitor and secure
viral isolates from humans infected with bird flu, they may be able
to map a mutation trajectory that will help predict when the avian
virus will cross the threshold to become a human pathogen.
The last two flu pandemics in 1957 and 1968 were caused by avian
viruses that had accumulated enough genetic mutations to be
considered hybrids of animal and human viruses, Kawaoka notes.