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Journal of Virology, August 2007, p. 7960-7973, Vol. 81, No. 15
0022-538X/07/$08.00+0 doi:10.1128/JVI.00536-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
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Institute of Human Virology, University of Maryland Biotechnology Center, Baltimore, Maryland 21201,1 Virginia Bioinformatics Institute at Virginia Tech, Blacksburg, Virginia 24061,2 Division of Pathology, Walter Reed Army Institute of Research, Silver Spring, Maryland 209103
Received 14 March 2007/ Accepted 6 May 2007
Acute arenavirus disease in primates, like Lassa hemorrhagic fever in humans, begins with flu-like symptoms and leads to death approximately 2 weeks after infection. Our goal was to identify molecular changes in blood that are related to disease progression. Rhesus macaques (Macaca mulatta) infected intravenously with a lethal dose of lymphocytic choriomeningitis virus (LCMV) provide a model for Lassa virus infection of humans. Blood samples taken before and during the course of infection were used to monitor gene expression changes that paralleled disease onset. Changes in blood showed major disruptions in eicosanoid, immune response, and hormone response pathways. Approximately 12% of host genes alter their expression after LCMV infection, and a subset of these genes can discriminate between virulent and nonvirulent LCMV infection. Major transcription changes have been given preliminary confirmation by quantitative PCR and protein studies and will be valuable candidates for future validation as biomarkers for arenavirus disease.
Published ahead of print on 23 May 2007.
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