Flu virus 'knows when to attack'

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Image caption,
How does a virus keep track of time?

The flu virus has an in-built clock which tells it exactly when to strike to have the maximum impact, a study in the Cell Reports journal shows.

The internal molecular clock tells the flu bug how much time it has to multiply, infect other cells, and spread to another human being.

If it attacks too early it will be too weak, but leave it too late and the immune system has time to fight back.

Researchers say finding ways to reset the clock could lead to new treatments.

Study leader Prof Benjamin tenOever, from Mount Sinai School of Medicine in New York, said once inside a human cell, the virus needed to steal resources in order to multiply and gain a foothold.

This can alert the immune system to the virus' presence, so how does the flu virus know how much time it has got left, he added.

Accumulates protein

The researchers discovered that the virus slowly accumulates one particular protein called NEP that it needs to exit the cell and spread to other cells - and eventually other humans.

To stop itself making too much NEP the virus has linked its production with that of another protein NS1.

They then manipulated this timer by making the virus acquire this protein too fast. This caused flu to exit the cell too quickly and not have time to make more of itself.

On the other hand acquiring this protein too slowly would give the immune system time to launch a response before the virus can escape - killing the virus and preventing infection, they said.

Prof tenOever hopes this discovery will lead to new antiviral drugs which target the virus's internal clock and that it will provide a new design platform for the flu vaccine.

"We knew that the virus has about eight hours in a cell to create enough copies of itself to continue spreading before the cell's antiviral alarm would be set off," he said.

"On a broader level, the virus needs two days of continuous activity to infect enough cells to permit spread to another human being.

"We wanted to tap into the flu's internal clock and find a way to dismantle it to prevent the spread of the virus."

Prof Wendy Barclay, chair in influenza virology at Imperial College London, said other more complex viruses make proteins at different times during replication, but what is clever is that influenza can do this in such a simple way.

"It is tempting to speculate that drugs might be developed that disrupt the regulation of these two viral proteins and drive the virus to make too much NEP too early, thus bringing the infection to an untimely halt."

But she said cautioned against being too enthusiastic because the flu virus may well find a way to reset its timer.

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