La Jolla (02/29/04)- The virus that caused the 1918 flu pandemic
has features more closely
linked to avian (bird) viruses than to flu viruses that are more adapted
to infecting humans. Details of the similarities provide researchers with
for developing flu vaccines, and add insight into the origin of flu viruses
it into the human population.
One thing many people don't realize is that "all flus have their origins
from birds," said Ian Wilson, PhD, a molecular biologist at the Scripps
Research Institute. Most pandemics originally come from water fowl such as
But viruses don't easily jump between different species, and when they do
it takes time for them to adapt so they can easily infect humans.
The many strains of influenza circulating through the human population are
variations of the same handful of avian viruses that successfully did make
the leap, and have been around for decades. Over time the viruses mutate,
and vaccines need to be updated in order
to be effective
in protecting against them. Avian flu has been in the news because of recent
human cases reported in Thailand and China. While viruses don't normally
jump between species very
easily, certain conditions increase the risk.
"People who are getting infected
now in Thailand are working very closely with thousands of chickens in
crowded conditions. There is a high titer of virus going around there, and
sort of dose can cause some severe problems in the infected person,"
Dr. Wilson said. Even when a person is infected with an avian virus, it "is
not human-adapted and can't be passed on to another human."
However, in rare cases the virus can become human-adapted, but this also
requires special conditions. This occurs when a person with avian flu is
simultaneously infected with a strain of flu that is already human-adapted.
The two flu viruses infect the same cells where they grow and reproduce,
and while they are in such close quarters can swap genetic information. This
swapping of genetic information is what microbiologists call "reassortment".
If the avian virus ends up with genetic changes that allow it to bind to
human receptors in the respiratory tract or lungs, then the virus can be
easily passed on from person to person.
The appearanace of a new reassorted virus is rare, but is believed to have
happened three times in recent history; in the 1918, 1957 and 1968 influenza
pandemics. The 1918 influenza pandemic had a high death rate because protective
flu vaccines, and anti-bacterial agents designed to fight subsequent pneumonia
were not available. The pandemic killed more than 20-million people
Tissue biopsies from soldiers who died from the 1918 influenza, stored at
the Armed Forces Institute of Pathology, were made available to the researchers.
Analyses showed that the structure of the virus "looks like an avian
virus with some modifications that made it human-adapted," Dr. Wilson
said. Findings were published in the journal Science.
A feature on the virus surface, the hemagglutinin membrane
glycoprotein (HA) gave researchers the biggest clue that this was a new avian-related
virus. HA "is very important to a virus. It contains the receptor binding
site to enable the virus to stick to our cells," he said. HA also contains
another site that allows the virus membrane to fuse to the surface of cells
in the upper respiratory tract so that the virus can work its way into a
cell. These are changes that allow the bird virus to infect human cells.
Viruses invade host cells in order to reproduce.
Importantly, the HA had a site on its surface that can bind to avian
cells and cause infection. It had additional structures that tend to
be found in avain viruses, but not in viruses that are more human-adapted.
These mostly avian features would contribute to the virus being more infective
and deadly to humans since the human immune system would have trouble recognizing
and killing it. Knowing what the structure of the 1918 influenza virus is
like can be used to create vaccines should a similar virus emerge in the