Editor's Comment: Type I interferons, also known as alpha and beta interferon, are upregulated during viral infections. It has long been thought that Type I interferons are powerful antiviral agents. However, this study reveals that Type I interferons actually perpetuate chronic viral infections by suppressing effective antiviral immune reponses. By blocking Type I interferons, the researchers found that although circulating virus was higher for the first few days of infection, it was cleared much faster, preventing the infection from becoming chronic. Dr. Paul Cheney observed many years ago that patients with CFS have high levels of alpha interferon. For a more in-depth discussion of this significant finding, please read the article in Science Daily.
Persistent LCMV Infection Is Controlled by Blockade of Type I Interferon Signaling
By John R. Teijaro et al.
During persistent viral infections, chronic immune activation, negative immune regulator expression, an elevated interferon signature, and lymphoid tissue destruction correlate with disease progression. We demonstrated that blockade of type I interferon (IFN-I) signaling using an IFN-I receptor neutralizing antibody reduced immune system activation, decreased expression of negative immune regulatory molecules, and restored lymphoid architecture in mice persistently infected with lymphocytic choriomeningitis virus. IFN-I blockade before and after establishment of persistent virus infection resulted in enhanced virus clearance and was CD4 T cell–dependent. Hence, we demonstrate a direct causal link between IFN-I signaling, immune activation, negative immune regulator expression, lymphoid tissue disorganization, and virus persistence. Our results suggest that therapies targeting IFN-I may help control persistent virus infections.
Source: Science 12 April 2013: Vol. 340 no. 6129 pp. 207-211 DOI: 10.1126/science.1235214. John R. Teijaro1, Cherie Ng, Andrew M. Lee, Brian M. Sullivan, Kathleen C. F. Sheehan, Megan Welch, Robert D. Schreiber, Juan Carlos de la Torre, Michael B. A. Oldstone