Signalling pathways that initially orchestrate potent antiviral attacks can, paradoxically, also help to sustain chronic infections.

Proteins called type I interferons (IFN-I) curb viral replication during early stages of infection, but are unable to clear chronic infections. To solve this long-standing puzzle, independent groups led by David Brooks at the University of California, Los Angeles, and Michael Oldstone at the Scripps Research Institute in La Jolla, California, studied mice infected with strains of lymphocytic choriomeningitis virus that cause chronic infection.

Both groups found that IFN-I produces an initial burst of antiviral activity, but then depresses the immune system over the long term, allowing the virus to persist.

Chronic activation of the immune system can damage tissue, and the authors speculate that IFN-I signalling dampens the immune-system response to limit this damage. Inhibiting IFN-I signalling may help to control chronic viral infections, they say.

Science 340, 202–207; 207–211 (2013)