Public Release: 

New Evidence Shows How Some Flu Viruses Become Lethal

University of Wisconsin-Madison

MADISON, Wisc. -- Studying a descendant of the 1918 influenza virus that killed at least 20 million people worldwide, University of Wisconsin-Madison virologists discovered a new molecular trick some viruses use to transform from dangerous to deadly.

In research detailed in the Aug. 18 Proceedings of the National Academy of Sciences, UW-Madison virologists Hideo Goto and Yoshihiro Kawaoka have found a molecular mechanism that allows influenza viruses to cause sweeping damage throughout the body. Influenza infection is normally limited to respiratory systems, but this previously undetected process gives the virus the deadly ability to attack many organs in the body.

"This finding provides an additional marker for scientists to be aware of in their surveys of emerging viruses," said Kawaoka. "This could be another important indicator of whether a virus is dangerous and potentially lethal."

Kawaoka said the extreme virulence of the 1918 influenza virus is a public health mystery. One of the worst infectious disease outbreaks in human history, the 1918 flu killed not only vulnerable populations such as the elderly and young children, but an unusually high number of otherwise healthy young adults.

While this finding offers no definitive explanation for the 1918 virus, Kawaoka said it is a question that warrants further scientific study.

Kawaoka and Goto, researchers in the UW-Madison School of Veterinary Medicine, studied a virus closely related to the 1918 strain which appeared nearly a decade later in humans. The virus is widely studied for its ability to replicate in the brains of mice, but Kawaoka also found it could replicate in a number of different organs.

Their discovery concerns proteins on the virus' surface that allow the virus to attach to target cells. Normally, a viral surface protein called hemagglutinin must be chopped into two parts before the virus can infect a cell. The virus uses an enzyme from the cell it is invading to clip the protein.

The enzyme that acts as a "scissors" is normally localized in respiratory organs, which confines the virus to that part of the body. But in this strain of virus, Goto and Kawaoka found a unique mechanism at work that could lead to more widespread infection.

A different surface protein on the virus, called neuraminidase, binds and traps a common enzyme precursor called plasminogen, and this union created a molecular key that gave the virus access to cells throughout the body, rather than only the respiratory system.

"The importance of this finding is that it's the first example of a virus using a binding protein to its benefit when infecting a host," he said. "Our finding may have much broader implications in the virology field, and will prompt researchers to look for a protein of this kind in other viruses."

Influenza viruses are never the same threat each year. Their surface proteins normally undergo slight changes, called "drift," which requires new vaccines to be developed to protect against them. More dangerous is a "shift," when two different viruses mix together to create a radically different strain. A continual pursuit of virologists is to identify these shifts and drifts each year in order to develop effective vaccines.

The research was funded by National Institute of Allergy and Infectious Diseases (NIAID), a component of the National Institutes of Health. "[The researchers'] findings point us in a direction to better understand the pathology of these more virulent influenza viruses," said Dominick Iacuzio, program officer for influenza and related viral respiratory diseases at the NIAID.

For the full text of the article, contact Dave Schneier at the National Academy of Sciences news office at (202) 334-2138.

Written by Brian Mattmiller, (608) 262-9772


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