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| Status |
Public on Jun 08, 2010 |
| Title |
Gene expression associated with liver metabolism during viral hemorrhagic fever |
| Platform organism |
Homo sapiens |
| Sample organism |
Macaca mulatta |
| Experiment type |
Expression profiling by array
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| Summary |
Rhesus macaques (Macaca mulatta) infected with a lethal dose of lymphocytic choriomeningitis virus-strain WE (LCMV-WE) provide a model for Lassa fever virus infection of man. Like Lassa fever in human beings, disease begins with flu-like symptoms but can progress to morbidity fairly rapidly. Previously, we profiled the blood transcriptome of LCMV-infected monkeys (M. Djavani et al. J. Virol. 2007: PMID 17522210) showing distinct pre-viremic and viremic stages that discriminated between virulent and benign infections. In the present study, changes in liver gene expression from macaques infected with virulent LCMV-WE were compared to gene expression in uninfected monkeys as well as to monkeys that were infected but not diseased. We observed gene expression changes that occurred before the viremic stage of the disease, and could potentially serve as biomarkers that discriminate between exposure to a hemorrhagic fever virus and exposure to a benign virus. Based on a functional pathway analysis of differentially expressed genes, virulent LCMV-WE had a much broader effect on liver cell function than non-virulent virus. During the first few days of infection, virulent virus impacted gene expression associated with the generation of energy, such as fatty acid metabolism and glucose metabolism, with the complement and coagulation cascades, and with steroid metabolism, MAPK signaling and cell adhesion. For example, the energy profile resembled that of an organism entering starvation: acetyl-CoA carboxylase, a key enzyme of fatty acid synthesis, was shut down and gene products involved in gluconeogenesis were up-regulated. In conclusion, this study identifies several potential gene markers of LCMV-WE-associated liver disease and contributes to the database of gene expression changes correlated with LCMV pathogenesis in primates.
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| Overall design |
6 groups: uninfected controls, LCMV-WE infected (pre-viremic; day 1 to day 3), LCMV-WE infected (viremic; day 4 to day 7), LCMV-WE infected (post-viremic; day 8 to day 12), LCMV-Armstrong (LCMV-ARM; non-virulent strain) infected, and LCMV-ARM/LCMV-WE infected but not diseased. Each sample is from the liver of a different rhesus macaque.
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| Contributor(s) |
Djavani M, Crasta OR, Zhang Y, Zapata JC, Sobral B, Bryant J, Davis H, Salvato MS |
| Citation(s) |
19216742 |
| Submission date |
Jul 25, 2008 |
| Last update date |
Mar 25, 2019 |
| Contact name |
kommidi Reddy Chaitanya |
| E-mail(s) |
kommidi@vbi.vt.edu
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| Phone |
5402311986
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| Organization name |
VBI
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| Street address |
Virginia Tech
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| City |
Blacksburg |
| State/province |
VA |
| ZIP/Postal code |
24060 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (20)
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| GSM307741 |
LCMV-WE infected, day 1, sample 1 |
| GSM307742 |
LCMV-WE infected, day 1, sample 2 |
| GSM307743 |
LCMV-WE infected, day 2, sample 3 |
| GSM307744 |
LCMV-WE infected, day 3, sample 5 |
| GSM307745 |
LCMV-WE infected, day 4, sample 6 |
| GSM307746 |
LCMV-WE infected, day 4, sample 7 |
| GSM307747 |
LCMV-WE infected, day 6, sample 8 |
| GSM307748 |
LCMV-WE infected, day 6, sample 9 |
| GSM307749 |
LCMV-WE infected, day 7, sample 10 |
| GSM307914 |
LCMV-WE infected, day 11, sample 11 |
| GSM307915 |
LCMV-WE infected, day 12, sample 12 |
| GSM307916 |
LCMV-ARM infected but not diseased, day 3, sample 3 |
| GSM307917 |
LCMV-ARM infected but not diseased, day 5, sample 5 |
| GSM307918 |
LCMV-ARM/LCMV-WE infected but not diseased, sample 11 |
| GSM307919 |
LCMV-ARM/LCMV-WE infected but not diseased, sample 15 |
| GSM307920 |
LCMV-ARM/LCMV-WE infected but not diseased, sample 22 |
| GSM307921 |
LCMV-ARM/LCMV-WE infected but not diseased, sample 26 |
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| Relations |
| BioProject |
PRJNA113629 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE12254_RAW.tar |
91.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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