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Papers by Kim Loesch

Research paper thumbnail of Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus

Gastroenterology, 2002

Abbreviations used in this paper: ALT, alanine aminotransferase; BHT, butylated hydroxytoluene; B... more Abbreviations used in this paper: ALT, alanine aminotransferase; BHT, butylated hydroxytoluene; BrdU, 5-bromo-2-deoxyuridine; DAB, 3,3-diaminobenzidene tetrahydrochloride; DAPI, 4,6diamidino-2-phenylindole; HCC, hepatocellular carcinoma; MMLV, Maloney murine leukemia virus; RT-PCR, reverse-transcription polymerase chain reaction; SV40, simian virus 40.

Research paper thumbnail of Impaired clearance of virus-infected hepatocytes in transgenic mice expressing the hepatitis C virus polyprotein

Gastroenterology, 2004

Background & Aims: Multiple molecular mechanisms are likely to contribute to the establishment of... more Background & Aims: Multiple molecular mechanisms are likely to contribute to the establishment of persistent infection by hepatitis C virus (HCV). The aim of this work was to study the evasion of cell-mediated antiviral immune responses in transgenic mice with livertargeted expression of the hepatitis C viral genome. These mice develop steatosis and hepatocellular carcinoma and constitute a murine model of chronic HCV infection. Methods: Mice of the FL-N/35 lineage were infected with replication-deficient adenoviral vectors encoding ␤-galactosidase, and the persistence of infected cells was measured by histochemistry and enzymatic assays. Results: Hepatocytes from the HCV ؉ transgenic mice are deficient in eliminating an adenoviral infection, despite an apparently normal T-cell response. The defect in adenoviral clearance was associated with resistance of transgenic hepatocytes to apoptosis induced by Fas/ APO1/CD95 death receptor stimulation, a major pathway of cell killing by cytotoxic T lymphocytes. The attenuation of Fas-mediated apoptosis observed in the murine model was associated with a reduced abundance of Bid, a BH3-only member of the Bcl-2 family of apoptosis regulators. Conclusions: Our results suggest that viral evasion of cell-mediated immune responses leading to apoptotic death of hepatocytes may contribute to viral persistence. Such a mechanism might also contribute to the development of liver cancer in HCV.

Research paper thumbnail of Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus

Gastroenterology, 2002

Abbreviations used in this paper: ALT, alanine aminotransferase; BHT, butylated hydroxytoluene; B... more Abbreviations used in this paper: ALT, alanine aminotransferase; BHT, butylated hydroxytoluene; BrdU, 5-bromo-2-deoxyuridine; DAB, 3,3-diaminobenzidene tetrahydrochloride; DAPI, 4,6diamidino-2-phenylindole; HCC, hepatocellular carcinoma; MMLV, Maloney murine leukemia virus; RT-PCR, reverse-transcription polymerase chain reaction; SV40, simian virus 40.

Research paper thumbnail of Impaired clearance of virus-infected hepatocytes in transgenic mice expressing the hepatitis C virus polyprotein

Gastroenterology, 2004

Background & Aims: Multiple molecular mechanisms are likely to contribute to the establishment of... more Background & Aims: Multiple molecular mechanisms are likely to contribute to the establishment of persistent infection by hepatitis C virus (HCV). The aim of this work was to study the evasion of cell-mediated antiviral immune responses in transgenic mice with livertargeted expression of the hepatitis C viral genome. These mice develop steatosis and hepatocellular carcinoma and constitute a murine model of chronic HCV infection. Methods: Mice of the FL-N/35 lineage were infected with replication-deficient adenoviral vectors encoding ␤-galactosidase, and the persistence of infected cells was measured by histochemistry and enzymatic assays. Results: Hepatocytes from the HCV ؉ transgenic mice are deficient in eliminating an adenoviral infection, despite an apparently normal T-cell response. The defect in adenoviral clearance was associated with resistance of transgenic hepatocytes to apoptosis induced by Fas/ APO1/CD95 death receptor stimulation, a major pathway of cell killing by cytotoxic T lymphocytes. The attenuation of Fas-mediated apoptosis observed in the murine model was associated with a reduced abundance of Bid, a BH3-only member of the Bcl-2 family of apoptosis regulators. Conclusions: Our results suggest that viral evasion of cell-mediated immune responses leading to apoptotic death of hepatocytes may contribute to viral persistence. Such a mechanism might also contribute to the development of liver cancer in HCV.

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