Gene expression in primate liver during viral hemorrhagic fever

Djavani Mahmoud, Crasta, Zhang Yan, Zapata Juan, Sobral Bruno, Lechner, Bryant Joseph, Davis Harry, Salvato

Description

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-β. Conclusion 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.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2009
• Nombre de lectures: 8
• Langue: English

Extrait

Virology Journal

BioMedCentral

Open Access Research Gene expression in primate liver during viral hemorrhagic fever 1 22 1 Mahmoud Djavani, Oswald R Crasta, Yan Zhang, Juan Carlos Zapata, 2 31 1 Bruno Sobral, Melissa G Lechner, Joseph Bryant, Harry Davisand 1 Maria S Salvato*

1 2 Address: Instituteof Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA,Virginia Bioinformatics Institute 3 at Virginia Tech, Blacksburg, VA 24061, USA andUniversity of Southern California, Keck School of Medicine, Los Angeles, CA 90089, USA Email: Mahmoud Djavani  [e-mail]; Oswald R Crasta  [e-mail]; Yan Zhang  [e-mail]; Juan Carlos Zapata  [e-mail]; Bruno Sobral  [e-mail]; Melissa G Lechner  [e-mail]; Joseph Bryant  [e-mail]; Harry Davis  [e-mail]; Maria S Salvato*  [e-mail] * Corresponding author

Published: 12 February 2009Received: 12 January 2009 Accepted: 12 February 2009 Virology Journal2009,6:20 doi:10.1186/1743-422X-6-20 This article is available from: http://www.virologyj.com/content/6/1/20 © 2009 Djavani et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract 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-β. Conclusion: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.

Background Arenaviruses are rodentborne viruses that can be trans mitted to primates, occasionally causing lethal hemor

rhagic fever. Arenaviruses causing Lassa fever and South American hemorrhagic fevers have been classified as Cat egory A biothreats in the United States because of their

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