Scientists have discovered why some influenza viruses are transformed from dangerous to deadly.

The breakthrough may help doctors target potentially deadly viruses before they get out of control.

It has long been a mystery why some strains of flu turn into mass killers, claiming millions of lives worldwide.

The worst episode in history was the 1918 Spanish Flu pandemic in which between 20 and 40 million people died.

But scientists studying a descendent of the 1918 virus say they have identified a molecular mechanism that allows it to cause sweeping and potentially fatal damage to the body.

Unique key

The virus had a unique "key" which unlocked the door to cells throughout the body, enabling it to re-create itself in many different organs. Normally influenza is confined to cells within the respiratory system.

Lead researcher Dr Yoshihiro Kawaoka, from the University of Wisconsin School of Veterinary Medicine in Madison, in the United States, said: "This is a mechanism that we never knew existed in influenza viruses.

"Now we have additional markers that we can look for when a peculiar outbreak of human or animal flu occurs."

Attach to target cells

The discovery concerns proteins on the surface of the virus that allow it to attach to target cells.

Normally one of these proteins, called hemagglutinin, must be chopped into two parts before the virus can infect a cell. The virus uses enzymes from the cells it is invading as "scissors" to cut the protein.

These protease enzymes are usually found in the lungs and trachea, which is why influenza tends to be confined to that part of the body.

Greater movement

Some 'flu virus an infect the whole body

But in the strain studied by the scientists a different mechanism was at work that allowed the virus greater freedom of movement.

Another viral surface protein, called neuraminidase, had two distinct features that allowed it to bind and trap a common enzyme precursor chemical.

This substance, plasminogen, produced the enzyme plasmin, which could also execute the vital splitting of hemagglutinin. But plasminogen was obtainable from cells throughout the body, allowing the virus to spread beyond the respiratory system.

Ten other human, swine and bird viruses were also tested by the researchers but no evidence of the same mechanism was found.

The new discovery should allow doctors monitoring flu viruses to spot changes which might give a virus pandemic potential.

Writing in the Proceedings of the National Academy of Sciences, the researchers said any virus strain with the same characteristic neuraminidase molecules "should be regarded as potentially dangerous".

Frequent changes

Influenza virus surface proteins alter frequently, requiring new vaccines to be developed to protect against them.

The viruses are never the same each year, but normally the surface proteins undergo slight changes.

More dangerous is a "shift" when two different viruses mix together to create a radically different strain.