Cellular sources of interferon-beta in virus-infected organs of the mouse
Final Report Abstract
In summary, our project disclosed some novel insights into the role of IFNAR-mediated positive feedback regulation for robust IFN production in vivo. At the primary site of THOV infection, the peritoneal cavity, a cell population positive for the markers CD11b and F4/80, which most likely are peritoneal macrophages, could be identified as major producers of IFN‐β. We observed that mice lacking functional type I IFN receptors were still able to induce sustained IFN production after infection with THOV even in the absence of a positive feedback loop. However, infected Ifnar1-/- mice also showed strongly increased viral load compared to wildtype mice, suggesting that the massive viral replication in Ifnar1-/- mice might overcome the requirement of positive feedback regulation. When Ifnar1-/- animals were infected with replication-incompetent virus-like particles, IFN production was drastically diminished as compared to WT mice. These findings indicate that strong stimuli enable IFNAR-independent IFN production in vivo, whereas weak stimuli resulting for example from infection with replication-incompetent virus particles require amplification via positive feedback mechanisms.
Publications
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(2016). Cellular Sources of Beta-Interferon during Viral Infections and Mechanisms of its Induction in vivo. Doktorarbeit Fakultät für Biologie, Universität Freiburg
Pfefferkorn, C.
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Abortively infected astrocytes appear to represent the main source of interferon-β in the virus-infected brain. J. Virol. 90: 2031-2038 (2016)
Pfefferkorn, C., Kallfass, C., Lienenklaus, S., Spanier, J., Kalinke, U., Rieder, M., Conzelmann, K.-K., Michiels, T., & P. Staeheli
