Laboratorio de Biomedicina, FIMCM, Escuela Superior Politécnica del Litoral (ESPOL), Campus Gustavo Galindo, Km 30.5 via Perimetral, Apartado 09-01-5863, Guayaquil, Ecuador.
Viruses. 2010 Jan;2(1):262-282. doi: 10.3390/v2010262. Epub 2010 Jan 21.
The members of the filoviruses are recognized as some of the most lethal viruses affecting human and non-human primates. The only two genera of the Filoviridae family, Marburg virus (MARV) and Ebola virus (EBOV), comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central Africa, with case fatality rates ranging from 25 to 90%. Fatal outcomes have been associated with a late and dysregulated immune response to infection, very likely due to the virus targeting key host immune cells, such as macrophages and dendritic cells (DCs) that are necessary to mediate effective innate and adaptive immune responses. Despite major progress in the development of vaccine candidates for filovirus infections, a licensed vaccine or therapy for human use is still not available. During the last ten years, important progress has been made in understanding the molecular mechanisms of filovirus pathogenesis. Several lines of evidence implicate the impairment of the host interferon (IFN) antiviral innate immune response by MARV or EBOV as an important determinant of virulence. In vitro and in vivo experimental infections with recombinant Zaire Ebola virus (ZEBOV), the best characterized filovirus, demonstrated that the viral protein VP35 plays a key role in inhibiting the production of IFN-α/β. Further, the action of VP35 is synergized by the inhibition of cellular responses to IFN-α/β by the minor matrix viral protein VP24. The dual action of these viral proteins may contribute to an efficient initial virus replication and dissemination in the host. Noticeably, the analogous function of these viral proteins in MARV has not been reported. Because the IFN response is a major component of the innate immune response to virus infection, this chapter reviews recent findings on the molecular mechanisms of IFN-mediated antiviral evasion by filovirus infection.
丝状病毒成员被认为是影响人类和非人类灵长类动物的最致命病毒之一。丝状病毒科的两个属，马尔堡病毒（MARV）和埃博拉病毒（EBOV），是导致中非严重出血热爆发的主要病原体，病死率在 25%至 90%之间。致命结局与感染后免疫反应的延迟和失调有关，这很可能是由于病毒针对关键宿主免疫细胞，如巨噬细胞和树突状细胞（DC），这些细胞是介导有效的先天和适应性免疫反应所必需的。尽管在开发丝状病毒感染疫苗方面取得了重大进展，但仍没有用于人类的许可疫苗或治疗方法。在过去十年中，人们在理解丝状病毒发病机制的分子机制方面取得了重要进展。有几条证据表明，MARV 或 EBOV 对宿主干扰素（IFN）抗病毒先天免疫反应的损害是毒力的一个重要决定因素。用重组扎伊尔埃博拉病毒（ZEBOV）进行的体外和体内实验感染，这是最具特征的丝状病毒，表明病毒蛋白 VP35 在抑制 IFN-α/β的产生中起关键作用。此外，VP24 抑制细胞对 IFN-α/β的反应，协同增强 VP35 的作用。这些病毒蛋白的双重作用可能有助于病毒在宿主中进行有效的初始复制和传播。值得注意的是，MARV 中这些病毒蛋白的类似功能尚未报道。由于 IFN 反应是病毒感染先天免疫反应的主要组成部分，因此本章综述了丝状病毒感染逃避 IFN 介导的抗病毒作用的分子机制的最新发现。
