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1918 Flu Virus Resembled Bird Virus

By Pippa Wysong, Access Excellence

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 more information for developing flu vaccines, and add insight into the origin of flu viruses that make it into the human population.hemagglutinin structure

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 ducks. 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 that 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 worldwide

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 future.


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