MIT researchers gain new insight on how flu spreads from cell to cell in the body

Cholesterol molecules (green) binding to M2 influenza protein molecules (grey and purple). The shaded grey shapes represent what the configuration looks like on the surface.
An MIT team found that two cholesterol molecules bind to a flu protein called M2 to sever a viral bud from its host cell by narrowing the neck of the bud. Cholesterol molecules are shown in green, while the M2 viruses are shown in gray and purple. Two types of views are shown: One is of the surface of the neck, while the other shows a molecular diagram of it.

For the first time, MIT researchers say, they have been able to see how the flu virus spreads from cell to cell.

Previous studies have shown that a protein called M2 was involved in the separation of the flu virus from its host cell, as well as the fact that this action was dependent on cholesterol in the cell membrane. But no one had been able to explain what caused the separation, the university said. In fact, researchers had been unable to detect even the structure of the elusive M2.

But the MIT researchers have now detected the incredibly small and dynamic flu protein, said Mei Hong, a chemistry professor at MIT and the senior author of the study.


“What’s really cool, we didn’t expect this, was that . . . cholesterol binds to M2 in a one-to-two ratio, meaning one cholesterol to two proteins,” she said in a telephone interview Friday.

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The study, published in the journal Proceedings of the National Academy of Sciences, used solid-state nuclear magnetic resonance spectroscopy (a relative of the magnetic resonance imaging or MRI that doctors use) to detect signals from cells that indicate the structure and movements of molecules in them, Hong said.

“We can essentially image, in a sense, the protein’s molecular structures,” she said.

Using that technique, Hong and her team found that the one-to-two ratio was the key to understanding how the flu virus breaks free from its host cell, Hong said.

Once it’s infected a cell and has commandeered its inner workings, the virus makes copies of itself that gather into buds attached to the membrane, the university said. The buds then break free from their host and go on to infect other cells.


The researchers found that the buds break off after the cholesterol in the membrane binds with the M2 influenza proteins. The binding causes the buds to curve and narrow where they’re attached to the host until they break off, Hong said.

If the ratio between the cholesterol and the M2 proteins were even, there would be no asymmetry and the buds would not break off, Hong said.

Adding more cholesterol into human cells would help, but Hong and her team are not encouraging that because of the negative health impacts.

“We’re not advocating to add tons of cholesterol to the membrane,” she said.

The new research doesn’t have any direct implications for flu treatments, Hong said. Still, it could prove useful in understanding other proteins that interact with the cholesterol in cell membranes, including those involved in Alzheimer’s and Parkinson’s diseases.


“About 30 percent of proteins encoded by the human genome are associated with the cell membrane, so you’re talking about a lot of direct and indirect interactions with cholesterol,” Hong said. “And now we have a tool for studying the cholesterol-binding structure of proteins.”

Alyssa Meyers can be reached at [email protected]. Follow her on Twitter @ameyers_.