Interferon escape by measles and rabies virus

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Immune Escape of Rabies Virus and Measles Virus

Co-evolution of viruses with their hosts for millions of years has led to a host immune system of high complexity and, likewise, sophisticated viral mechanisms to antagonize immunity. Early cytokines, such as interferons (IFNs), which integrate innate and adaptive immune responses, are essential targets for viruses. Viral antagonists that interfere with numerous components of the IFN system provide superb tools to explore the pathways and the connectivity of the IFN network.

(From: Hengel H, Koszinowski UH and Conzelmann KK. Viruses know it all: new insights into IFN networks. Trends Immunol. 2005;26(7):396-401.)

Rabies virus (RV) and measles virus (MV) have developed different strategies to counteract the immune response of the host.

The phosphoprotein P of the neurotropic RV inhibits RLR-  as well as IFN-signaling and thereby prevents both the production (Brzózka et al. 2005) and the activity of IFNβ (Brzózka et al. 2006).

In contrast, the hematotropic MV gained functions to inhibit the TLR7/9-signaling cascade, which is responsible for IFNα production in specialized immune cells, the plasmacytoid dendritic cells (pDCs), by the non-structural V protein (Fig. 1A; Pfaller and Conzelmann 2008). In addition, multiple steps of the IFN-signaling cascade are inhibited by MV P and V.
NF-κB is activated upon stimulation of TLRs or RLRs in parallel to the IFN-inducing transcription factors IRF3 and 7 and triggers the expression of various cytokines. We currently investigate the role of MV proteins on this signaling cascade.