Harvard Researchers Discover Native Flu-Fighting Proteins

A team led by Harvard researchers has discovered a family of naturally occurring proteins in human cells that protect against influenza and other illnesses—a finding that may lead to methods to speed up vaccine production and to new flu prevention drugs for humans.

Shedding greater light on the human body’s first-line defense against the flu virus, the researchers found that the family of flu-fighting proteins—called the interferon-inducible transmembrane (IFITM) proteins—prevented or slowed down most virus particles from infecting human cells early in the lifecycle of the virus. The team reported its findings in an online journal on Thursday.

“Most of the time we find things that the virus needs,” said Abraham L. Brass, instructor in medicine at Harvard Medical School and Mass. General Hospital, who helped lead the study. “This time we found something our cells are using to resist the virus.”

The influenza virus—equipped with only eight genes of its own—hijacks the genetic material of its host cell, infecting and utilizing the human genes to execute the virus’ own operations, according to Stephen J. Elledge, a professor of genetics at Harvard Medical School and head of the lab in which the study took place. With this understanding, Elledge and his team systematically deactivated every gene in the human genome—testing some 20,000 different genes—using new RNA interference technology, hoping to determine the genes in the host cells that the virus relied upon for infection.

“We were trying to sabotage them by figuring out what they’re actually using and taking it away,” said Elledge, who is also a senior geneticist at Brigham and Women’s Hospital.

The researchers, who had already used this same process in studies of HIV and the hepatitis C virus, hoped to find that some of the treated cells could not be infected with the influenza virus, which would suggest that the virus needed the deactivated gene to function. Instead, the researchers were surprised to find that the rate of infection increased dramatically when certain genes were deactivated.

The study found that the family of proteins generated by these key genes, known as IFITM, plays a major role in protecting cells against the flu.

“There’s a certain level of it in your cells all the time preventing 80 to 90 percent of all infections,” Elledge said. “If you get rid of those genes, you see nine or 10 times more infections.”

Brass and Elledge said that they next seek to determine how IFITM works in preventing the flu. For now, the discovery of these native anti-viral proteins may bode well for the battle against influenza.

A drug that increases the presence of IFITM proteins in humans without provoking negative side effects may be an effective means of preventing influenza. Another area of potential research is the possibility of inserting the IFITM genes into the genomes of animals like swine and poultry—the strains of influenza most dangerous to humans typically emerge from these animals.

In addition, the discovery may help expedite the production of flu vaccines, according to Elledge. By deactivating the IFITM genes in laboratory cells, scientists could grow influenza vaccines in these cells much more quickly. The larger crop of viruses can then be used to produce more vaccines.

Further research revealed that the same proteins also help cells resist illnesses such as West Nile virus, dengue fever, and yellow fever. But the proteins did not seem to be effective in defending cells from HIV or hepatitis C.

—Staff writer Julie M. Zauzmer can be reached at jzauzmer@college.harvard.edu.