Seroepidemiological study in a Puumala virus outbreak area in South-East Germany.

Puumala virus (PUUV) is the cause of the majority of haemorrhagic fever with renal syndrome cases in Germany. In 2004, a nephropathia epidemica outbreak was recorded in Lower Bavaria, South-East Germany. For a seroepidemiological study in this region including the resident population at four locations (n = 178) and soldiers from one location (n = 208) indirect immunoglobulin M (IgM) and immunoglobulin G (IgG) enzyme-linked immunosorbent assays (ELISAs) and immunoblot tests based on a yeast-expressed PUUV nucleocapsid protein were established. The validation using human serum panels originating from Germany revealed a diagnostic sensitivity and specificity of 98/100% for the IgM ELISA, 99/99% for the IgG ELISA, 99/100% for the IgM immunoblot test and 100/96% for the IgG immunoblot test. Using the novel IgG assays as well as a commercial IgG ELISA and an immunofluorescence assay for the resident population an average prevalence of 6.7% (12 of 178) with a range of 0% (0 of 21) to 11.9% (7 of 59) was observed. Positive serological results were equally distributed between males and females with an average age of 63 for males and 52 for females. The seroprevalence in the soldier group was found to be about 1% with one positive male of 203 (age 46 years) and one positive female of five (age 47 years). In conclusion, the PUUV seroprevalence in the residents of the outbreak region in Lower Bavaria was found to be up to fivefold higher than the average hantavirus seroprevalence of the German population.

GAR22: a novel target gene of thyroid hormone receptor causes growth inhibition in human erythroid cells.

OBJECTIVE: Thyroid hormone receptors (TRs) are ligand-dependent transcription factors with a major impact on erythroid cell development. Here we investigated TR activity on red cell gene expression and identified TR target genes. The impact of the TR target gene GAR22 (growth arrest-specific 2 [GAS2]-related gene on chromosome 22) on red cell differentiation was determined. MATERIALS AND METHODS: Stem cell factor/erythropoietin (SCF/EPO)-dependent red cell progenitors were differentiated in vitro in the presence or absence of thyroid hormone. Hormone-induced changes in gene expression were measured by a genome-wide approach with DNA microarrays. Ectopic expression of the TR target gene GAR22 was used to determine its impact on red cell differentiation. RESULTS: Ligand-activated TR effectively accelerated red cell progenitor differentiation in vitro concomitantly with inducing growth arrest. We demonstrate that activated TR-induced specific gene expression patterns of up- or downregulated genes, including distinct clusters associated with accelerated differentiation in response to treatment. Mining for T3-induced genes identified basic transcription element binding protein 1/Krüppel-like factor 9 (BTEB1/KLF9) and GAR22 as TR target genes. BTEB1/KLF9 is a known TR target gene while GAR22, initially identified as a putative tumor suppressor, represents a novel TR target gene. We demonstrate that ectopic GAR22 expression in red cell progenitors lengthens the cell cycle and causes growth inhibition, but leaves red cell gene expression unaffected. CONCLUSION: This study identifies GAR22 as a novel and direct TR target gene. Our results suggest that hormone-induced GAR22 might represent an important trigger of growth inhibition induced by thyroid hormone in red cell progenitors.