Likewise, the induction of T cell, B cell and PD-1 pathway gene signatures in the liver of chronically infected chimpanzees are consistent with the intrahepatic expression patterns in the woodchuck model of CHB. The elevated expression of CXCL9 and ubiquitin D in the liver LBH589 price of chimpanzees with CHB also indicates that an intrahepatic type II IFN response is characteristic of persistent hepadnavirus infection in both woodchucks and chimpanzees. In contrast, the absence of a neutrophil transcriptional signature in chronically infected chimpanzees may represent an important difference between these animal models, and suggests they might reflect
different stages of HBV natural history in man. Conclusion: Chronic HBV infection in chimpanzees shares key features with CHB in man as well as woodchucks. Notably, this includes intrahepatic induction of the PD-1 pathway, which suggests that T cell exhaustion is a common feature of chronic hepadnavirus infection and likely contributes to viral persistence. Disclosures: Li Li – Employment: Gilead Sciences Peng Yue – Employment: Gilead Sciences Robert E. Lanford – Grant/Research Support: Arrowhead Research Congrong Niu – Employment: Gilead Science Stephane Daffis – Employment: Gilead
Sciences Daniel Tumas – Employment: Gilead Sciences, Inc Abigail Fosdick – Employment: Gilead Sciences William E. Delaney – Employment: Gilead Sciences; Patent Held/Filed: Gilead Sciences; Stock Shareholder: Gilead Sciences Simon P. Fletcher selleckchem – Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences The dramatic clinical course of ALF has hampered molecular pathogenesis studies. While in classic acute hepatitis B liver damage is believed to be T-cell mediated, the pathogenesis of HBV-associated ALF is unknown. By gene expression profiling, we previously demonstrated that ALF is characterized by a prominent selleck chemicals intrahepatic B-cell gene signature associated with overexpression of negative regulators of T-cell activation, including CTLA-4. The availability of 13 liver specimens from 4 well-characterized patients with HBV ALF who underwent liver transplant within 1
week of admission gave us the unique opportunity to study the whole set of 2226 human miRNAs (Affymetrix) in ALF and in individual specimens from 17 normal livers as controls. Our aim was to investigate the correlation between mRNA and miRNA expression, as well as serum cytokine profiles. A multivariate permutation F-test with a false discovery rate of 1% identified 111 miRNAs differentially expressed in ALF livers. To investigate the functional correlations between miRNAs and mRNAs, first we performed two independent analyses using Ingenuity. Seven major disease categories were significantly associated with both mRNA and miRNA expression in ALF, with inflammatory and immunological diseases among the most prominent, demonstrating that mRNAs and miRNAs are strongly correlated.