Geisbert Thomas W, Hensley Lisa E
Department of Viral Pathology and Ultrastructure, Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702-5011, USA.
Expert Rev Mol Med. 2004 Sep 21;6(20):1-24. doi: 10.1017/S1462399404008300.
Ebola virus (EBOV) gained public notoriety in the last decade largely as a consequence of the highly publicized isolation of a new EBOV species in a suburb of Washington, DC, in 1989, together with the dramatic clinical presentation of EBOV infection and high case-fatality rate in Africa (near 90% in some outbreaks), and the unusual and striking morphology of the virus. Furthermore, there are no vaccines or effective therapies currently available. Progress in understanding the origins of the pathophysiological changes that make EBOV infections of humans so devastating has been slow, primarily because these viruses require special containment for safe research. However, an increasing understanding of the mechanisms of EBOV pathogenesis, facilitated by the development of new tools to elucidate critical regulatory elements in the viral life cycle, is providing new targets that can be exploited for therapeutic interventions. Notably, identifying factors triggering the haemorrhagic complications that characterise EBOV infections led to the development of a strategy to modulate coagulopathy; this therapeutic modality successfully mitigated the effects of EBOV haemorrhagic fever in nonhuman primates. This review summarises our current understanding of EBOV pathogenesis and discusses various approaches to therapeutic intervention based on our current understanding of how EBOV produces a lethal infection.
埃博拉病毒(EBOV)在过去十年中广为人知,主要是由于1989年在华盛顿特区郊区新分离出一种埃博拉病毒,引起了高度关注,同时埃博拉病毒感染的临床症状严重,在非洲的病死率很高(在某些疫情中接近90%),而且该病毒的形态异常显著。此外,目前尚无疫苗或有效疗法。由于这些病毒的研究需要特殊的安全防护措施,因此在理解导致人类埃博拉病毒感染如此致命的病理生理变化起源方面进展缓慢。然而,随着用于阐明病毒生命周期中关键调控元件的新工具的开发,人们对埃博拉病毒发病机制的理解不断加深,这为治疗干预提供了新的靶点。值得注意的是,确定引发埃博拉病毒感染特征性出血并发症的因素,促成了一种调节凝血障碍策略的制定;这种治疗方式成功减轻了非人灵长类动物感染埃博拉病毒出血热的影响。本综述总结了我们目前对埃博拉病毒发病机制的理解,并根据我们目前对埃博拉病毒如何导致致命感染的理解,讨论了各种治疗干预方法。