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University of Louisville

Electronic Theses and Dissertations

2016

AML-12

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Pro-Inflammatory Cytokines Promote Viral Replication And Cell Cycle Mediators In Arenavirus-Induced Hepatitis., Gretchen E. Holz Dec 2016

Pro-Inflammatory Cytokines Promote Viral Replication And Cell Cycle Mediators In Arenavirus-Induced Hepatitis., Gretchen E. Holz

Electronic Theses and Dissertations

Lassa virus (LASV) is an arenavirus and causative agent of Lassa fever (LF), a viral hemorrhagic fever in West Africa for which there is no vaccine. Lymphocytic choriomeningitis virus (LCMV), is used as a surrogate to mimic LASV-induced liver pathology. LCMV-WE, not LCMV-ARM, causes disease in primates and mice characterized by hepatitis, high viral load, hepatocyte proliferation, and upregulated proliferative triggers (e.g. TNF-α, IL-6 ). We hypothesize LCMV-WE induces pathological hepatocyte proliferation via pro-inflammatory triggers (TNF-α, IL-6) from macrophages, leading to: increased viral replication, modulated cell cycle, and arrested cell cycle. RAW 264.7 macrophages and AML-12 hepatocytes, were used as …