ABSTRACT: The chimpanzee is the only model other than man for investigating the pathogenesis of viral hepatitis types A through E. Studies of the host response, including microarray analyses, have relied on the close relationship between these two primate species: chimpanzee samples are commonly tested with human-based reagents. In this study, the host response to two dissimilar viruses, hepatitis E virus (HEV) and hepatitis C virus (HCV), was compared in multiple experimentally-infected chimpanzees. Affymetrix U133+2.0 human microarray chips were used to assess the entire transcriptome in serial liver biopsies obtained over the course of the infections. The comparison utilized a permutational t-test-based analysis of selected time points. More specifically, baseline samples were compared with post-inoculation samples that were strategically chosen based on their relationship to viremia, and probe sequences were aligned to the human and chimpanzee genome sequences to assess their relative sensitivity for detecting differentially expressed genes. Regardless of the viral infection, the alignment of differentially expressed genes to the human genome sequence resulted in a larger number of genes being identified when compared with alignment to the chimpanzee genome sequence. This probably reflects the lesser refinement of gene annotation for chimpanzees. In general, the two viruses demonstrated very distinct temporal changes in host response genes, although both RNA viruses induced genes that were involved in many of the same biological systems, including interferon-induced genes. The host response to HCV infection was more robust than the response to HEV infection. Three chimpanzees were inoculated intravenously with the hepatitis C virus: chimp 1628 was infected with < 100 infectious doses (ID) of the H77 strain (genotype 1a) (30); chimp 1417 was infected with an unknown titer, in serum, of the HC-J6 strain (genotype 2a) (31); chimp 1422 was infected with an unknown titer, in serum, of the T.N. strain (genotype 1a) (35). Four chimpanzees (CH1616, CH1618, CH1374 and CH1375) were inoculated intravenously with 0.5 ml of the HEV SAR55 strain (genotype 1) at approximately 10^6 ID. Grouping of the biological replicates was based on viremia: groups consisted of the first positive week (and the second positive week for HCV), the peak positive week, the last positive week, the first negative week and the fourth negative week. There were 3 biological replicates for HCV. The 4 replicates for HEV were both biological and technical. For chimp 1417, 7 samples were taken between weeks 0 and 17. For chimp 1422, 8 samples were taken between weeks 0 and 13. For chimp 1628, 8 samples were taken between weeks 0 and 19. For chimp 1374, 6 samples were taken between weeks 0 and 8. For chimp 1375, 4 samples were taken between weeks 0 and 8. For chimp 1616, 5 samples were taken between weeks 0 and 7. For chimp 1618, 6 samples were taken between weeks 0 and 8. Normalized probe set level data not provided for individual Sample records. Processed data is available on Series record.
