Gene expression in primate liver during viral hemorrhagic fever.
BACKGROUND
Rhesus macaques infected with lymphocytic choriomeningitis virus (LCMV) provide a model for human Lassa fever. Disease begins with flu-like symptoms and progresses rapidly with fatal consequences. Previously, we profiled the blood transcriptome of LCMV-infected monkeys (M. Djavani et al J. Virol. 2007) showing distinct pre-viremic and viremic stages that discriminated virulent from 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.


RESULTS
Based on a functional pathway analysis of differentially expressed genes, virulent LCMV-WE had a broader effect on liver cell function than did infection with non-virulent LCMV-Armstrong. During the first few days after infection, LCMV altered expression of genes associated with energy production, including fatty acid and glucose metabolism. The transcriptome profile resembled that of an organism in starvation: mRNA for acetyl-CoA carboxylase, a key enzyme of fatty acid synthesis was reduced while genes for enzymes in gluconeogenesis were up-regulated. Expression was also altered for genes associated with complement and coagulation cascades, and with signaling pathways involving STAT1 and TGF-beta.


CONCLUSIONS
Most of the 4500 differentially expressed transcripts represented a general response to both virulent and mild infections. However, approximately 250 of these transcripts had significantly different expression in virulent infections as compared to mild infections, with approximately 30 of these being differentially regulated during the pre-viremic stage of infection. The genes that are expressed early and differently in mild and virulent disease are potential biomarkers for prognosis and triage of acute viral disease.
Djavani
Mahmoud
M
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. mdjavani@ihv.umaryland.edu
Crasta
Oswald R
OR
Zhang
Yan
Y
Zapata
Juan Carlos
JC
Sobral
Bruno
B
Lechner
Melissa G
MG
Bryant
Joseph
J
Davis
Harry
H
Salvato
Maria S
MS
D000818:Animals; D001117:Arenaviridae Infections / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008217:Lymphocytic choriomeningitis virus / Q000472:pathogenicity*; D008253:Macaca mulatta; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
D011506:Proteins