In conclusion, based on the increased IL-18 expression levels in psoriatic skin lesions relative to uninvolved skin, this cytokine appears to be crucial in the development of the active psoriatic lesion itself, where it is produced locally by a step in the evolution of the psoriatic lesion. This could be supported by its correlation with clinical severity and disease duration, and reduction of its expression after treatment. The decreased expression after treatment was not to an extent indicating that the skin had returned to normal. The small size of the study population and the heterogeneous group of patients participating in the study preclude the drawing of firm conclusions. Future studies on genes involved and array-based technologies should allow confirmation of the results obtained. Also further studies are recommended to try other lines of treatment for psoriasis. One of these lines of therapy is to try r-h IL-18 BP to neutralize IL-18 activity on a wide scale that will ultimately lead to improved outcomes for patients. Replication enhancer elements within the open reading frame of tick-borne encephalitis virus and their evolution within the Flavivirus genus We provide experimental evidence of a replication enhancer element (REE) within the capsid gene of tick-borne encephalitis virus (TBEV, genus Flavivirus). Thermodynamic and phylogenetic analyses predicted that the REE folds as a long stable stem–loop (designated SL6), conserved among all tick-borne flaviviruses (TBFV). Homologous sequences and potential base pairing were found in the corresponding regions of mosquito-borne flaviviruses, but not in more genetically distant flaviviruses. To investigate the role of SL6, nucleotide substitutions were introduced which changed a conserved hexanucleotide motif, the conformation of the terminal loop and the base-paired dsRNA stacking. Substitutions were made within a TBEV reverse genetic system and recovered mutants were compared for plaque morphology, single-step replication kinetics and cytopathic effect. The greatest phenotypic changes were observed in mutants with a destabilized stem. Point mutations in the conserved hexanucleotide motif of the terminal loop caused moderate virus attenuation. However, all mutants eventually reached the titre of wild-type virus late post-infection. Thus, although not essential for growth in tissue culture, the SL6 REE acts to up-regulate virus replication. We hypothesize that this modulatory role may be important for TBEV survival in nature, where the virus circulates by non-viraemic transmission between infected and non-infected ticks, during co-feeding on local rodents. Tick-borne encephalitis virus (TBEV) is a human pathogen that causes about 16 000 human cases of tick-borne encephalitis (TBE) across Europe and Asia annually (1) (2) (3) . Taxonomically, TBEV is a species within the mammalian tick-borne flaviviruses (mTBFV). Together with the seabird tick-borne flavivirus group (sTBFV), they comprise one ecological group of tick-borne flaviviruses (TBFV) within the genus Flavivirus, family Flaviviridae. Two other ecological groups within the genus Flavivirus are the mosquito-borne flaviviruses (MBFV) and flaviviruses with no-known vector (NKV) (4) . A fourth group including Kamiti River virus (KRV) (5) , cell fusion agent virus (CFAV) (6) and Culex flavivirus (CuFV) (7) have been isolated only from mosquitoes with no demonstrated capacity to replicate in mammals and are under consideration by the ICTV Committee for classification as 'probably arthropod-borne viruses' (PABV).