This week we focus on tracking the avian virus through birds, the
spread of the virus through wild birds and a recent report detailing
large-scale sequencing of viral genomes.
Tracking of influenza
It may be news to many, but scientists have been tracking avian
influenza for five years. Vincent Munster at the Erasmus Medical
Center in Rotterdam runs a large surveillance program, getting more
than 8,000 samples a year. Understandably, their work has become of
great interest to the world at large because of the avian influenza
outbreak. More about this work is detail in the October 21st issue of
Science
(Vol 310, issue 5747, pp 428). An interesting note from the
article, between 1 and 20% of all captured ducks are infected with
influenza, most without symptoms.
The spread of H5:N1
Avian flu experts have been almost universally skeptical that
H5:N1 could be spread by wild birds, instead feeling that most spread
was taking place by domestic bird sale and transport. One reason is
that sampling of ten of thousands of wild birds has yet to turn up a
single healthy wild bird carrying the H5:N1 strain. Wild ducks and
geese can be infected with the virus, but it is just as lethal to
them as it is to chickens. Since dead ducks don't fly, it seemed
unlikely they would spread the virus very far after being infected.
That conventional wisdom appears to be about to change. The death of
100 or so ducks, gulls, geese and swans at a remote lake in Mongolia
has surprised scientists and forced them to reexamine the role of
wild birds. This lake has no domestic bird population or human
activity that could have brought the virus to the area. In an
interesting twist, it appears surveillance crews were looking at the
wrong birds, species known to be susceptible to the virus appear not
to be the carriers, but some as-yet unidentified wild species. The
implication is huge, H5:N1 will spread across the world through wild
populations and there is little that can currently be done to stop
it, since we do not know the identity of the carrier.
Some other interesting tidbits I picked up in the readings.
Influenza viruses are subtyped based on the forms of hemagglutinin
(H) and neuraminidase (N) in their outer membrane. There are 16 H and
9 N forms known. Viruses are further classified by their
pathogenicity. Low-pathogenicity viruses infect a birds respiratory
and digestive tract, while highly pathogenic strains will spread
through all cells in the body, usually causing death. Almost all
combinations of H and N have been found as low-pathogenicity strains
in birds, including non-lethal strains of H5:N1. It is thought that
during the jump from water fowl to chickens and turkeys that the
viruses adapt and emerge as highly pathogenic strains. Highly
pathogenic bird influenzas have emerged 19 times since 1959, causing
flu epidemics in poultry. The latest outbreak is of note because of
the number of humans that have come down with the illness. H5:N1 also
has the disquieting property of also being capable of killing
waterfowl. Last April, at Lake Qinghai, China, an estimated 5,000 to
6,000 migratory water birds were killed by the virus.
Large-scale sequencing of influenza viruses
Ghedin et al. in the October
20th issue of Nature describe a protocol for the
sequencing of large numbers of influenza A viruses and they use this
technique to sequence 209 complete genomes. Before this paper only 7
complete genomes were known for the influenza virus and these were
only of highly pathogenic strains. The authors use RT-PCR, if anyone
is curious I can explain it in the comments section, to characterize
viruses circulating in the New York area over a five year period.
These viruses were mostly of the H3:N2 variation, a very common
influenza virus that infects humans.
This analysis gives the first picture of how influenza viruses
evolve over time. One of the more dramatic findings involved the
detection of a reassortment. In earlier work the authors showed that
at any time there are several genetically distinct clades (a group of
organisms thought to have evolved from a common ancestor) circulating
in a population. Ghedin et al. detected the donation of hemagglutinin
from a minor clade to a major clade, causing the creation of a noval
viral strain. The flu vaccine in use at the time provided very little
defense against this new viral strain.
The research also shows the change of influenza viral strains over
time, with mutant variants that appear in one flu season becoming the
dominant strains in the next flu season. By following these changes
over time, we may get a clearer picture of what residues are
important in infection. It may be possible therefore to better
predict what the dominant viral strains will be and which ones will
cause more serious illness. These same concepts could be applied to
avian strains. It may be possible by comparing H5:N1 viruses to human
viruses to determine what sequences need to change for a progeny
virus to be capable of transmission from human to human. The authors
state at the end of the paper that they plan to apply their technique
to avian influenza strains.
As a side note, PubMed, the journal searching site, has a new
feature where you can save your search criteria as an RSS feed and
check up on changes using your news reader. Mighty cool.