Cellular miRNAs are key regulators in posttranscriptional regulat

Cellular miRNAs are key regulators in posttranscriptional regulation of gene expression. They can also directly participate in virus replication or act indirectly

by determining the expression level of replication cofactors. To analyze whether the commonly used Huh7 cell lines differ in their miRNA expression patterns, we screened 883 human miRNAs using the Geniom Biochip miRNA Homo sapiens (febit holding gmbh, Heidelberg, Germany). PHHs isolated from human liver resections of two check details different patients were used as reference. Figure 1 and Supporting Table 1 show the profound differences not only between PHHs and hepatoma cell lines but also between the cell lines. Remarkably, the liver-specific miRNA122 that directly influences HCV replication both in cell culture and in infected chimpanzees2-4 was one of the most differentially expressed miRNAs. Furthermore, predictions of the gene targets of the miRNAs from Fig. 1A by the Genetrail program (freely accessible at http://genetrail.bioinf.uni-sb.de) identified a number of host proteins whose differential expression is known or expected to influence HCV replication (see Supporting Table 2 for the complete target list). Because studies on host factor requirements for virus replication nowadays involve small interfering RNA–mediated

down-regulation of candidate proteins, and the level of knockdown is influenced by protein abundance and turnover and thus miRNA composition, one would expect that the respective experimental results would be influenced by the host cells used. The recent observations of nonoverlapping screening R788 cell line results for HCV host factors5 may well be related to corresponding

miRNA differences in the host cells. Michael Ehrhardt*, Petra Leidinger Ph.D.†, Andreas Keller Ph.D.†, Thomas F. Baumert Megestrol Acetate Ph.D.‡ §, Juana Díez Ph.D.¶, Eckart Meese Ph.D.†, Andreas Meyerhans Ph.D.* **, * Departments of Virology, Saarland University, Homburg, Germany, † Human Genetics, Saarland University, Homburg, Germany, ‡ Institut National de la Santé et de la Recherche Médicale, Unité 748, § Université de Strasbourg, Strasbourg, France, ¶ Molecular Virology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain, ** ICREA Infection Biology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain. Additional Supporting Information may be found in the online version of this article. “
“Chronic hepatitis B (CHB) is a variable, dynamic disease and accounts for significant morbidity and mortality. Long-term disease outcome data in infancy-acquired patients stratified according to HBV genotype, HBeAg status, HBV DNA and HBsAg levels are limited. Plasma levels of chemokine IP10 predict HBeAg/HBsAg seroconversion in CHB adults.

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