TSRI scientists find interferon initiates viral infection

Scientists at The Scripps Research Institute in La Jolla, California, recently discovered that a human protein thought to be a powerful antiviral agent may induce persistent viral infection and limit an effective immune response.

The study, which was published in Friday's Science, found that type 1 interferon proteins initiated persistent infection in mice and limited the generation of an effective antiviral immune response. Since its discovery more than 50 years ago, IFN-I was thought to be a powerful antiviral agent that controlled the immune response against foreign invaders.

"Our findings illuminate an unexpected role for IFN-I protein(s) in persistent infections, which has major implications for how we treat these infections," Michael Oldstone, a senior investigator in the study, said.

For years, scientists assumed that the production of IFN-I proteins by immune cells known as dendritic cells was part of a healthy immune system reaction to a viral infection. When the TSRI researchers blocked the IFN-I-alpha-beta receptor, however, they found a drop in production of interleukin-10 and PD-1, immune-suppressing proteins that act as a braking system to balance the immune response. Over the long term, blocking the IFN-I-a-b receptor brought a stronger immune response for clearing out a viral infection.

"Even when we blocked IFN-I-a-b receptor after a persistent infection had been established and T-cell exhaustion had set in, we still saw a significantly earlier clearance of the virus," Cherie Ng, one of the first authors of the study, said.

Oldstone and his colleagues plan to study IFN-I signaling pathways in further detail in an effort to determine if the IFN-I-a-b receptor blocking strategy can work on chronic viral infections in humans.

If successful, the strategy could be used to improve the immune response against viral infections such as hepatitis B, hepatitis C, chronic HIV, human papillomavirus, Epstein-Barr virus and cytomegalovirus.