Human Protein Prevents H1N1 Replication

The unexpected discovery—made by a team led by Stephen J. Elledge and Abraham Brass, HHMI—that human cells respond to H1N1 infection by increasing production of these proteins that block replication of the above-mentioned viruses could lead to development of more effective antiviral agents.

The proteins, from Interferon-Inducible Transmembrane family (IFITM1, IFITM2, and IFITM3), have been known since 1984 to be produced at low levels in most cells and at higher levels in those that were exposed to immune-stimulation interferon proteins; however, researchers hadn’t understood their functions until the current study.

When Elledge’s team saw that disruption of IFITM3 resulted in surprising increases in H1N1 replication, they suspected that the proteins had natural antiviral effects. “The virus replicated five to ten times better when IFITM3 wasn't there," said Elledge. "The viral protein level was higher and it would replicate faster. IFITM3 really stood out in this regard.” After finding the same results in different cell types and with different H1N1 strains, the researchers decided to instead increase production of IFITM3 in cells and found that H1N1 replication was completely blocked. Although the strongest and most consistent effects were seen with IFITM3, overproduction of IFITM1 and IFITM2 could also block H1N1 and all other tested strains of the influenza A virus type.

However, the IFITMs weren’t able to fight off all tested viruses, with the researchers unsure what the proteins evolved to do precisely. “They have different levels of activity on their own, so they might be more specific for different types of viruses," Elledge said.

More work needs to be done to determine if exposing cells to higher than normal levels of the IFITMs for days or weeks, but Elledge said that it’s “possible that you could deliver it directly to the surface of cells, and have protective effects during flu season, for example.”

A new study conducted by researchers at Howard Hughes Medical Institute (HHMI), Harvard Medical School, Massachusetts General Hospital, Yale Medical School, and the Wellcome Trust Sanger Institute in Cambridge, UK—originally begun to identify which host proteins the H1N1 virus requires in order to enter cells and replicate inside them—has resulted in the finding that a naturally occurring human protein can help prevent infection not only by H1N1, but by other viruses like West Nile and dengue.