Flu checks its biological clock to evade detection

Flu is an insidious virus. It penetrates your cells, replicates and escapes to infect other cells before your immune system even knows that it is there.

Now we know how it times things so well. Like any good thief, flu uses a clock so it can do its dirty work and abscond before it's caught.

The timing mechanism could be a potential new target for anti-flu drugs, and more importantly, could help us make safer flu vaccines.

Benjamin tenOever and colleagues at the Mount Sinai Hospital in New York City wanted to find out how flu decides when to jump ship.

A gene's prerogative

They found that one of the virus's genes carries a sequence that controls how the gene is translated into a protein ? but it is very capricious.

Mostly the gene makes one main protein, but sometimes it will make another, called a nuclear export protein (NEP). Using microRNA molecules that inhibit specific bits of the gene, the team were able to slow down or speed up the production of NEP.

The researchers then watched as the virus failed to infect colonies of lung cells in culture.

When NEP was made too slowly, says tenOever, the immune response was able to catch up with the virus before it spread to more cells. When it was made faster, however, the virus abandoned the cell before it had multiplied sufficiently to infect other cells.

That means that NEP is flu's alarm clock. "The flu virus has about 8 hours to do enough replicating to spread effectively, before the immune system is alerted," says tenOever. NEP accumulates at just the right rate, and once a certain amount is present in the cell, it stops the virus making the protein and makes it pack up to leave, at just the right time.

Broken clock

"This is why flu is nastier than cold viruses, which don't do this," he says. "The virus can infect a large expanse of lung tissue before your immune system wakes up." It is also why someone can give you flu before they have symptoms.

A flu virus with a defective timing mechanism could be the basis for a new type of flu vaccine. Most flu vaccines available today contain the dead virus.

A vaccine based on a live, weakened virus is available, and can be more effective, but it cannot be given to the very young or old because of the risk that it might become dangerous in people with weaker immune systems. Yet these are the people who are most at risk of dying from flu.

TenOever hopes a flu virus with a defective clock might be even weaker and unlikely to ever cause disease, making it a safe, live vaccine.

Journal reference: Cell Reports, http://dx.doi.org/10.1016/j.celrep.2012.12.010

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