GENE FROM 1918 VIRUS PROVES KEY TO VIRULENT INFLUENZA

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" Lori Price " <lrprice

Tue, 11 Oct 2005 23:55:05 -0700 (PDT)

GENE FROM 1918 VIRUS PROVES KEY TO VIRULENT INFLUENZA

 

 

 

http://www.news.wisc.edu/releases/10241.html

 

News

Releases

FOR IMMEDIATE RELEASE

 

10/6/2004

 

CONTACT: Yoshihiro Kawaoka, (608) 265-4925, kawaokay

 

NOTE TO PHOTO EDITORS: High-resolution images are available at

http://www.news.wisc.edu/newsphotos/influenza.html

 

 

 

 

 

 

GENE FROM 1918 VIRUS PROVES KEY TO VIRULENT INFLUENZA

 

MADISON - Using a gene resurrected from the virus that caused the 1918

Spanish influenza pandemic, recorded history's most lethal outbreak of

infectious disease, scientists have found that a single gene may have

been responsible for the devastating virulence of the virus.

 

Writing Oct. 7 in the journal Nature, virologist Yoshihiro Kawaoka of

the University of Wisconsin-Madison and the University of Tokyo,

describes experiments in which engineered viruses were made more

potent by the addition of a single gene. The work is evidence that a

slight genetic tweak is all that is required to transform mild strains

of the flu virus into forms far more pathogenic and, possibly, more

transmissible.

 

The results of the new work promise to help scientists understand why

the 1918 pandemic, a worldwide outbreak of influenza that killed 20

million people, spread so quickly and killed so efficiently, says

Kawaoka, who has studied influenza viruses for 20 years. The finding

also lends insight into the ease with which animal forms of the virus,

particularly avian influenza, can shift hosts with potentially

catastrophic results.

 

" Replacing only one gene is sufficient to make the virus more

pathogenic, " says Kawaoka, a professor of pathobiological sciences at

the UW-Madison School of Veterinary Medicine. In the Nature paper,

Kawaoka and his colleagues describe how a Spanish flu gene that codes

for a key protein changed a relatively benign strain of flu virus from

a nuisance to a highly virulent form.

 

In the late 1990s, scientists were able to extract a handful of genes

from the 1918 virus by looking in the preserved lung tissue of some of

the pandemic's victims. Subsequently, the genes were sequenced,

including two critical genes that make hemagglutinin and

neuraminidase, the protein keys that help the virus enter and infect

cells.

 

Using a comparatively mild form of influenza A virus as a template,

Kawaoka's team added the two 1918 genes that code for hemagglutinin

and neuraminidase and infected mice with the engineered viruses.

 

" Here we demonstrate that the [hemagglutinin] of the 1918 virus

confers enhanced pathogenicity in mice to recent human viruses that

are otherwise non-pathogenic in this host, " Kawaoka and his colleagues

write in the Nature report. Moreover, the viruses with the 1918

hemagglutinin gene caused symptoms in the mice - infection of the

entire lung, inflammation and severe hemorrhaging - eerily similar to

those exhibited by human victims of the 1918 pandemic.

 

Scientists and historians have long speculated about why the 1918

Spanish flu virus was so virulent. Theories range from lack of modern

medical care and antibiotics, which had not yet been developed, to the

already weakened state of many victims due to war and the tumultuous

social conditions of the time.

 

" There also were people who thought the virus was different in terms

of its virulence, " Kawaoka says. The results of the new study tend to

support the idea that the virus was inherently more dangerous.

 

Another important result of the new study is that it supports the idea

that the 1918 Spanish flu virus was avian in origin, but already

adapted to proliferate in humans. That insight is important as

scientists and public health officials view birds as a primary

reservoir of influenza A virus, strains of which can sometimes jump

species to infect other animals, including humans.

 

According to Kawaoka, it's known that avian strains of the virus have

slightly different receptors - key proteins on the surface of the

virus that act like a key to unlock and infect host cells - from those

on flu viruses that infect humans.

 

" That restricts transmission from avian species (to humans) to some

extent, but not completely, " Kawaoka notes.

 

The receptors on the virus with the gene from the 1918 virus, Kawaoka

says, readily recognized their complements on human cells. " That tells

you that there was a change in receptor recognition after introduction

from avian species to humans. It recognized the human receptor even

though it came from an avian species. That's why it transmitted so

efficiently among humans. "

 

A third and intriguing finding of the study is that blood from the now

very elderly survivors of the 1918 pandemic had high antibody titers

to the engineered virus, Kawaoka says.

 

" People who were infected with this virus in 1918 still have high

antibodies, even after 80 years, " he says.

 

That scientifically interesting finding, Kawaoka explains, suggests

that another outbreak of flu like the 1918 pandemic would spare many

very old people who had had a brush with the virus more than 80 years

ago. The irony in that, according to Kawaoka, is that influenza often

extracts its heaviest toll on the elderly.

 

###

 

- Terry Devitt (608) 262-8282, trdevitt

 

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