During persistent viral infections, a dysregulated immune response fails to control the infection. Wilson et al. and Teijaro et al. (see the Perspective by Odorizzi and Wherry) show that this occurs because type I interferons (IFN I), critical for early responses to viral infection, contribute to the altered immunity seen during persistent infection. Antibody blockade of IFN I signaling during chronic lymphocytic choriomeningitis virus (LCMV) in mice resulted in reduced viral titers at later stages of infection, reduced expression of inhibitory immune molecules, and prevented the disruptions to secondary lymphoid organs typically observed during persistent infection with LCMV. Whether type I IFNs are also detrimental to persistent viral infection in humans, such as HIV and hepatitis C virus, remains to be determined.
E. B. Wilson, D. H. Yamada, H. Elsaesser, J. Herskovitz, J. Deng, G. Cheng, B. J. Aronow, C. L. Karp, D. G. Brooks, Blockade of chronic type I interferon signaling to control persistent LCMV infection. Science 340, 202–207 (2013). [Abstract] [Full Text]
J. R. Teijaro, C. Ng, A. M. Lee, B. M. Sullivan, K. C. F. Sheehan, M. Welch, R. D. Schreiber, J. C. de la Torre, M. B. A. Oldstone, Persistent LCMV infection is controlled by blockade of type I interferon signaling. Science 340, 207–211 (2013). [Abstract] [Full Text]