Int. J. Environ. Res. Public Health 2010, 7 954 Exact mechanisms of such Solar regulating influences are not completely understood yet. In our opinion, infra-annual immune-regulatory and epidemic-predisposing solar effects to a great extent are mediated and can be explained by the concomitant geomagnetic field fluctuations. Indeed, bio-regulatory capabilities of the magnetic fields and pertinent mechanisms have been described in the first four paragraphs of this paper. Moreover, regular semiannual variations in the geomagnetic field (Figure 1, bottom right panel) greatly resemble seasonal variations in viral respiratory diseases sickness rate, which allows speculation about the possible role of the geomagnetic field fluctuations as both flu epidemics and seasonal flu- predisposing factors. 7. Probable Mechanisms of the Geomagnetic Field and Solar Cycles Influences on Biological Functions and Virus-Host Interactions Following from the previous discussions, it is possible to predict some magnetic field-sensitive processes in living systems related to virus replication and host antiviral resistance. We can not consider all the pertinent mechanisms, but will focus here mainly on NF-κB-dependent pathways that play a key role in immune reactions, including response to infection. NF-κB is a protein complex that acts as a transcription factor. It is widely expressed and positively regulates the expression of genes involved in immune responses, inflammation, proliferation, apoptosis and other cellular activities. Initial steps of these pathways include nuclear translocation of NF-κB dimers, where they bind to specific κB sequences in the promoter or enhancer regions of multiple target genes, including those encoding proinflammatory cytokines, adhesion molecules, interferon, pro-apoptotic molecules, etc. (reviewed in [96,97]). Role of the NF-κB pathway in influenza infection is especially significant because NF-κB signaling plays an important role in differential regulation of influenza virus RNA synthesis [98]. These authors showned that overexpression of the p65 molecule (member of NF-κB subfamily) could activate influenza virus RNA transcription from the cRNA. And vice versa: siRNA-mediated knockdown of p65 protein significantly reduced influenza A virus replication and synthesis of most vRNA segments. NF-κB inhibitors: - decrease influenza virus production in infected cells and viral gene expression; - block early stages of the influenza virus life cycle; - specifically decrease the vRNA level during influenza virus infection [98]. Is it possible that Solar cycles and geomagnetic field perturbations can influence the NF-κB signaling pathway or mechanisms of virus replication, or both? The answer is “Yes”. It was already shown that magnetic field can affect translation processes in bacteria [99]. Expression of virus DNA integrated into cells can be affected by EM fields as well. For example, exposure of SV40-transformed human fibroblasts to magnetic field resulted in increased levels of virally derived mRNA and virus-specific protein [100]. Understanding of mechanisms underlying these phenomena would be very important. We predict several possible ways in which magnetic fields can modify gene expression, alter the NF-κB signaling and thus, influence virus-host interactions (Figure 11). First, it should be noted that genes encoding proteins of Rel/NF-κB/IκB pathway belong to an extensive set of clock-controlled genes [101]. As such, they are exposed to transcriptional regulation by the CLOCK/BMAL1 complex,