PROTEOME AND TRASCRIPTOME ANALYSIS OF HEMORRHAGIC FEVER IN CYNOMOLGUS MACAQUES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 丝状病毒马尔堡是几种暴发情况下持续存在的潜在生物威胁因子。它们的高死亡率和人与人之间传播的能力，加上缺乏疫苗、治疗和诊断方法，在自然爆发、输入和生物恐怖主义方面令人关切。马尔堡在安哥拉的重新出现（世卫组织最新报告）继续提醒我们注意非洲地区的疾病潜力。由于丝状病毒的宿主仍未确定，因此暴发预测和控制非常困难。由于气溶胶化病毒具有传染性，并且仅需要少量病毒粒子就具有传染性，因此丝状病毒被认为是潜在的生物武器。由于一些库存和创造它们的科学家仍然下落不明，马尔堡病毒是当今最严重的生物威胁之一。因此，我们迫切需要使生物威胁的可能性合理化。 观察到某些马尔堡出血热暴发导致不同程度的死亡率，这表明更强的毒株可能改变宿主对感染的反应。宿主反应是高度复杂的，涉及大量的细胞类型。我们假设这些细胞类型中宿主转录组和蛋白质组反应的差异可用于表征感染和鉴定致病性改变的马尔堡变体。这些配置文件将提供一个更深层次的理解生物威胁潜力的含义在几个分子水平内的主机响应程序。此外，我们相信，多因素分析将准确地确定基因型改变负责改变生物威胁表型。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The filovirus Marburg is a persistent and looming biothreat agent for several outbreak scenarios. Their high fatality rate and capacity for person to person transmission, combined with a lack of vaccines, therapeutics and diagnostics, are cause for concern in natural outbreaks, importation and bioterrorism. The re-emergences of Marburg in Angola (latest WHO report) continues to remind us of the disease potential in regions of Africa. Since the filoviral host reservoir(s) still remain(s) unidentified, outbreak prediction and control are very difficult. Since aerosolized virus is infectious and only a few virions are required for infectivity, filoviruses are regarded as potential bioweapons. Since some of the stockpiles and the scientists who created them remain unaccounted for, Marburg virus represents one of the most serious biothreats today. Consequently, there is an urgent need for us to rationalize the biothreat potentials. The observation that certain outbreaks of Marburg hemorrhagic fever result in varying degrees of mortality suggests that more virulent strains may alter the host response to infection. The host response is highly complex and involves a large number of cell types. We hypothesize that the differences in host transcriptome and proteome responses within these cell types can be used to characterize infection and identify Marburg variants with altered pathogenicity. These profiles will provide a deeper understanding of the meaning of biothreat potential at several molecular levels within the host response program. Furthermore, we believe that a multifactorial profiling will accurately identify genotypic alterations responsible for altered biothreat phenotype.