Fig. 5

Determination of the canonical NF-kB and IRF3/7 signalling pathways and the effects of lithium post RVFV infection. TLR 2 and 4 are stimulated by the viral glycoproteins that in turn recruit adapter molecule Myd88 via tirap. The adapter molecules recruit Irak4 which phosphorylate recruit irak-1 which then associate with Traf-6. Traf-6 recruit Tak1 and Tab2. Tak1 phosphorylate IΚΚ-β, which then phosphorylate IkB which is then tagged for ubiquitination and then degradation by cytoplasmic proteases. This then allows translocation of NF-kB to the nucleus and inflammatory genes expression. The RIG-1 is known to be stimulated by dsRNA from replicating viral genome, which is said to be hidden from the TLR-3. This cytoplasmic receptor is shown to be essential for viral IFN expression. The RIG-1 is shown to associate with IPS-1 with its N-terminal card domain. The IPS-1 and RIG-1 association activate TBK1 and IΚΚ-ε which phosphorylate IRF-3 and 7. The NSs is suggested to interfere with the IFN signalling at the transcription factor level since there is an expression of other inflammatory mediators except for IFNs. Since, the NSs inhibit the interferon production via IRF inhibition other transcription factors such NF-kB continue to produce inflammatory mediators, hence, elevated production of other inflammatory mediators except the IFN. This diagram suggests that NF-kB inhibition as a result of upregulated IkB could be the, mechanism in which lithium restore dysregulated inflammation after RVFV infection leading to haemorrhagic fever pathogeneses observed during this viral infection