HCV alters sphingolipid metabolism.

<p>(<b>A, B</b>) Time-course studies of humanized chimeric mice inoculated with human serum samples positive for HCV genotype 1a (<b>A</b>) or 2a (<b>B</b>). (<b>C</b>) mRNA expression of <i>SGMS1</i> and <i>SGMS2</i> in uninfected (white, n = 5) and HCV genotype 1a-infected (black, n = 7) chimeric mice. (<b>D, E</b>) Effects of HCV infection on hepatocyte SM and ceramide levels in humanized chimeric mice. Relative intensity of total ceramide (<b>D</b>) and total shingomyelin (SM) (<b>E</b>) in uninfected mouse hepatocytes (white bar, n = 4), HCV genotype 1a-infected mouse hepatocytes (black bar, n = 5), and HCV genotype 2a-infected mouse hepatocytes (dark gray bar, n = 3). (<b>F</b>) Mass spectrum of SM in Bligh & Dyer extracts of a human hepatocyte cell line (HuH-7 K4). (<b>G, H</b>) Effects of HCV infection on hepatocyte SM and ceramide levels in humanized chimeric mice. Relative intensity of individual ceramide molecular species (<b>G</b>) and individual SM molecular species (<b>H</b>) in uninfected mouse hepatocytes (white bar, n = 3), HCV genotype 1a-infected mouse hepatocytes (black bar, n = 3), and HCV genotype 2a-infected mouse hepatocytes (dark gray bar, n = 3). In all cases, error bars indicate SDs. *<i>p</i><0.05 and **<i>p</i><0.01 compared with uninfected hepatocytes.