The screen revealed more than 120 genes with potential roles in different stages of infection. Four of those genes, when knocked down, allowed for a robust increase in the infection of cells by influenza A virus. Of these four candidate "restriction factors," the research team concentrated on the IFITM3 protein because of its known link to interferon and found two closely related proteins in the IFITM family with similar activity.

The most distinctive property of the first-line IFITM3 defense is its preventive action before the virus can fuse with the cell, said co-author and virologist Michael Farzan, associate professor of microbiology and molecular genetics at HMS and the New England Primate Research Center. "The virus is unable to make a protein in the cell to counteract the IFITM proteins, because the cell is already primed against the virus," Farzan said. "To find something that hits the flu and hits it so close to the entry stage of the viral life cycle is really interesting and unusual among viral restriction factors."

The researchers have more questions than answers about how the IFITM restriction factors actually work, but they are excited about the range of inquiry the discovery opens up. For example, variations in the protein from person to person may explain differences in people's susceptibility to flu and other viral infections, as well as its severity, the researchers speculate.

And if scientists can understand the mechanism of action, they may be able to design new therapies with even better antiviral actions. The proteins themselves may be useful for defending against infections in animals, like birds and pigs, which might prevent the emergence of new, potentially more dangerous influenza A strains.

In another potential application, if IFITM3 has a role in the chicken embryos or canine cells used to make flu vaccines, inhibiting the proteins may speed up vaccine production, which has been an issue this year with the manufacture of the H1N1 pandemic vaccine.