JC virus antibody status in a pediatric multiple sclerosis cohort: prevalence, conversion rate and influence on disease severity.

BACKGROUND: Because of the emergence of novel therapies for multiple sclerosis (MS) and the associated increased risk of progressive multifocal leukoencephalopathy, John Cunningham (JC) virus infection has become a focus of interest for neurologists. However, little is known about JC virus infection in pediatric MS to date. OBJECTIVE: We aimed to analyze the prevalence of anti-JC virus antibodies, the conversion rate and the influence of the anti-JC virus antibody status on the clinical course in a large pediatric MS cohort. METHODS: Anti-JC virus antibodies were analyzed in serum samples within six months of disease onset and during the course of the disease. Clinical data were extracted from a pediatric MS databank. RESULTS: A total of 51.6% of 256 patients were found to be positive for anti-JC virus antibodies at onset of disease. No correlation between antibody status and clinical course was seen. Analyzing 693 follow-up serum samples revealed high titer stability, and an annual conversion rate of 4.37% was seen. CONCLUSION: No evidence was found that seropositivity for anti-JC virus antibodies influences the clinical course. Surprisingly, seroprevalence for anti-JC virus antibodies was more than twice as high as anticipated in this age group, raising the question of whether the infection increases the risk of MS development.

SMC condensation centers in Bacillus subtilis are dynamic structures.

SMC and MukB complexes consist of a central SMC dimer and two essential binding partners, ScpA and ScpB (MukE and MukF), and are crucial for correct chromosome compaction and segregation. The complexes form two bipolar assemblies on the chromosome, one in each cell half. Using fluorescence recovery after photobleaching (FRAP), we provide evidence that the SMC complex has high exchange rates. This depends to a considerable degree on de novo protein synthesis, revealing that the bacterial SMC complex has high on and off rates for binding to the chromosome. A mutation in SMC that affects ATPase activity and results in exaggerated DNA binding in vitro causes a strong segregation defect in vivo and affects the localization of the entire SMC complex, which localizes to many more sites in the cell than under normal conditions. These data indicate that ATP turnover is important for the function of Bacillus subtilis SMC. In contrast, the centromere protein Spo0J and DNA gyrase showed much less exchange between distinct binding sites on the chromosome than that seen with SMC. Binding of Spo0J to the origin regions was rather static and remained partially conserved until the next cell cycle. Our experiments reveal that the SMC complex has a high, condensin-like turnover rate and that an alteration of the ATPase cycle affects SMC function in vivo, while several nucleoid-associated proteins feature limited or slow exchange between different sites on the nucleoid, which may be the basis for epigenetic-like phenomena observed in bacteria.