H1N1 prevented by natural human protein

A naturally occurring human protein which could help slow transmission of H1N1, or even prevent infection by the virus, could lead to the development of more effective anti-viral drugs.

Lead investigator Stephen J Elledge began to suspect the protein had natural antiviral properties after the disruption of IFITM3 produced unusual results in H1N1 replication. “The virus replicated five to ten times better when IFITM3 wasn’t there.  The viral protein level was higher and it would replicate faster,” he said.
The influenza virus only has a few genes of its own, so – like other viruses – it hijacks proteins produced by its host to complete its lifecycle.  Researchers set up large arrays of cultured human cells and used a robotic device to deliver small strands of siRNA to each array.  The siRNA was designed to block expression of individual genes, and production of proteins.  The device recorded the effect on H1N1 activity by measuring the change in the presence of viral protein on the surface of infected cells.
Researchers identified over 120 genes whose expression is required for H1N1 to infect cells.  The gene for IFITM3 lies on chromosome 11 – next to similar genes for IFITM1 and IFITM2.  Although IFITM3 has the strongest and most consistent effects in testing, all three proteins can block H1N1 and other strains of Influenza A virus if overproduced.
However, the IFITMs are not effective against every virus tested, and the researchers are not sure what these proteins have evolved to do.  “They have different levels of activity on their own, so they might be more specific for different types of viruses,” Elledge said.
Researchers are not sure how the proteins are able to block viruses, but believe it may be because the proteins sit partly outside a cell’s membrane.  Elledge suggests that IFITMs cause molecules bought in through the cell membrane – such as viruses – to be routed to a disposal area where they are degraded.
High levels of IFITMs may not be safe for people in the long run, but Elledge suggests that they may become the basis for antiviral therapy in the future: “It’s possible that you could deliver it directly to the surface of cells, and have protective effects during flu season.”