Nuclear factor kB (NF-kB) transcription factors are key regulators in both insect and mammalian innate immune responses. Upon immune stimulation, degradation of the inhibitor of NF-kB (IkB) leads to nuclear localization of the transcription factor and transcriptional activation of antimicrobial peptides in the case of Drosophila (see Chapter 2 in this volume). Pathways under NF-kB transcrip-tional control have also shown to be involved in development and cellular immunity.
The exciting discovery that all PDV genomes sequenced so far encode IcB-like proteins, which lack the regulatory domains for signal-mediated degradation, led to the very attractive hypothesis that PDV IcBs could be acting as irreversible inhibitors of host NF-kB signalling.
So far, the evidence that parasitoid wasps could be affecting NF-kB signalling in Lepidoptera is quite sparse. For instance, double infection experiments involving parasitization followed by bacterial inoculation leads to normal induction of known anti-microbial peptides (Shelby et al., 1998; E. Huguet, unpublished results). However, after bacterial challenge of H. virescens larvae parasitized by T. nigriceps NF-kB immunoreactive proteins failed to enter the nucleus of host haemocytes and fat body cells (Falabella et al., 2007), suggesting that parasitism can indeed target these pathways. TnBV and MdBV IcB-like proteins were shown to reduce NF-cB-driven expression of reporter gene contructs in Hela cells and S2 cells respectively (Thoetkiattikul et al, 2005; Falabella et al, 2007). Furthermore, co-immunoprecipitation experiments indicated that MdBV H4 and N5 IcBs bound to Drosophila Dif and Relish NF-kB proteins. In the presence of these MdBV IcBs electrophoresis mobility shift assays (EMSAs) showed that Drosophila Dif and Relish were no longer capable of binding to kB sites (Thoetkiattikul et al., 2005). Collectively these data show that PDV IcBs have the potential to disrupt NF-kB signalling in lepidopteran hosts. The challenge will now be to demonstrate this effect and the immune or developmental consequences in vivo. Interestingly, immunofluorescence experiments using antibodies directed against two CsIV IcBs revealed these proteins localized to the nucleus of haemocytes and fat body post-parasitization, suggesting a possible functional role of PDV IcBs in the nuclei of infected lepidopterans (Kroemer and Webb, 2005).
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