Djavani Mahmoud M, Crasta Oswald R, Zapata Juan Carlos, Fei Zhangjun, Folkerts Otto, Sobral Bruno, Swindells Mark, Bryant Joseph, Davis Harry, Pauza C David, Lukashevich Igor S, Hammamieh Rasha, Jett Marti, Salvato Maria S
Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard St., Baltimore, MD 21201, USA.
J Virol. 2007 Aug;81(15):7960-73. doi: 10.1128/JVI.00536-07. Epub 2007 May 23.
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 non-virulent 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.
灵长类动物的急性沙粒病毒病，就像人类的拉沙热一样，始于类似流感的症状，并在感染后约两周导致死亡。我们的目标是确定血液中与疾病进展相关的分子变化。静脉注射致死剂量淋巴细胞性脉络丛脑膜炎病毒（LCMV）的恒河猴为人类感染拉沙病毒提供了一个模型。在感染前和感染过程中采集的血样用于监测与疾病发作平行的基因表达变化。血液变化显示类花生酸、免疫反应和激素反应途径出现重大紊乱。约12%的宿主基因在LCMV感染后改变其表达，其中一部分基因可区分毒性和非毒性LCMV感染。主要转录变化已通过定量PCR和蛋白质研究得到初步证实，未来作为沙粒病毒病生物标志物进行验证时，这些变化将是有价值的候选对象。
