Sequence analysis of the Ebola virus genome: organization, genetic elements, and comparison with the genome of Marburg virus

Sanchez, Anthony; Kiley, Michael P.; Holloway, Brian P.; Auperin, David D.

doi:10.1016/0168-1702(93)90063-s

Cited by 288 publications

(225 citation statements)

References 43 publications

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“…The genome encodes seven structural proteins, with a gene order of: 3' leader, nucleoprotein (NP), virion protein (VP) 35 (VP35), VP40, glycoprotein (GP), VP30, VP24, polymerase L protein, and 5' trailer (Ref. 14). Four of these proteins -NP, VP30, VP35 and L -associate with the genomic RNA in a ribonucleoprotein complex, while the three remaining proteins (GP, VP24 and VP40) are associated with the membrane.…”

Section: Ebov: Structure and Protein Functionsmentioning

confidence: 99%

Ebola virus: new insights into disease aetiopathology and possible therapeutic interventions

Geisbert

Hensley

2004

Expert Rev. Mol. Med.

111

106

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Ebola virus (EBOV) gained public notoriety in the last decade largely as a consequence of the highly publicised 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.

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Section: Ebov: Structure and Protein Functionsmentioning

confidence: 99%

Ebola virus: new insights into disease aetiopathology and possible therapeutic interventions

Geisbert

Hensley

2004

Expert Rev. Mol. Med.

111

106

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“…A unique feature of filovirus transcription start signals is that they are predicted to form stable RNA secondary structures [52,54]. The function of most predicted RNA structures remains to be determined.…”

Section: Filovirus Transcriptionmentioning

confidence: 99%

Filovirus Replication and Transcription

2007

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The highly pathogenic filoviruses, Marburg and Ebola virus, belong to the nonsegmented negative-sense RNA viruses of the order Mononegavirales. The mode of replication and transcription is similar for these viruses. On one hand, the negative-sense RNA genome serves as a template for replication, to generate progeny genomes, and, on the other hand, for transcription, to produce mRNAs. Despite the similarities in the replication/transcription strategy, filoviruses have evolved structural and functional properties that are unique among the nonsegmented negativesense RNA viruses. Moreover, there are also striking differences in the replication and transcription mechanisms of Marburg and Ebola virus. This includes nucleocapsid formation, the structure of the genomic replication promoter, the protein requirement for transcription and the use of mRNA editing. In this article, the current knowledge of the replication and transcription strategy of Marburg and Ebola virus is reviewed, with focus on the observed differences.

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“…EBOV and MARV have simple genomes that encode seven proteins, with the EBOV genome also encoding for a single additional nonstructural protein [10][11][12]. Within the nucleocapsid of each virion, a single copy of the viral genome is associated with the nucleoprotein (NP), virion protein (VP)30 and VP35 (FIGURE 1B).…”

Section: Biology Of Filovirus Infectionsmentioning

confidence: 99%

“…EBOV and MARV have simple genomes that encode seven proteins, with the EBOV genome also encoding for a single additional nonstructural protein [10][11][12].…”

Section: Biology Of Filovirus Infectionsmentioning

confidence: 99%

Filovirus-like particles as vaccines and discovery tools

Warfield

Swenson

Demmin

et al. 2005

Expert Review of Vaccines

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Ebola and Marburg viruses are members of the family Filoviridae, which cause severe hemorrhagic fevers in humans. Filovirus outbreaks have been sporadic, with mortality rates currently ranging from 30 to 90%. Unfortunately, there is no efficacious human therapy or vaccine available to treat disease caused by either Ebola or Marburg virus infection. Expression of the filovirus matrix protein, VP40, is sufficient to drive spontaneous production and release of virus-like particles (VLPs) that resemble the distinctively filamentous infectious virions. The addition of other filovirus proteins, including virion proteins (VP)24, 30 and 35 and glycoprotein, increases the efficiency of VLP production and results in particles containing multiple filovirus antigens. Vaccination with Ebola or Marburg VLPs containing glycoprotein and VP40 completely protects rodents from lethal challenge with the homologous virus. These candidate vaccines are currently being tested for immunogenicity and efficacy in nonhuman primates. Furthermore, the Ebola and Marburg VLPs are being used as a surrogate model to further understand the filovirus life cycle, with the goal of developing rationally designed vaccines and therapeutics. Thus, in addition to their use as a vaccine, VLPs are currently being used as tools to learn lessons about filovirus pathogenesis, immunology, replication and assembly requirements.Expert Rev. Vaccines 4(3), 429-440 (2005) Ebola (EBOV) and Marburg (MARV) viruses are the only members of the family Filoviridae, and were named according to their filamentous shape. EBOV and MARV cause acute and rapidly progressive hemorrhagic fever with mortality rates in humans of up to 90% [1,2]. The reservoir for filoviruses is unknown, although the consumption of monkey meat is often associated with onset of disease. Animals ranging from insects to mammals have been analyzed in the hopes of identifying a carrier, but to no avail [3]. After exposure, the onset of clinical symptoms can be as short as 2 days and as long as 21, although most infected humans and nonhuman primates die within 7-10 days of exposure [4]. In addition to hemorrhage and bleeding, other symptoms of filovirus infection include fever, headache, generalized myalgia, prostration, conjunctivitis, rash, lymphadenopathy, pharyngitis and edema [5].Filoviruses are considered serious public health threats, and are classified as biosafety level (BSL)-4 agents and Category A biothreat agents by the US Centers for Disease Control and Prevention [6,101]. Features that characterize filoviruses as a significant global health risk include high morbidity and mortality rates, potential for person-to-person transmission, relative stability in the environment, and feasibility of large-scale production. Additionally, the filoviruses have a low infectious dose, an extremely rapid rate of replication and can be easily transmitted, including via aerosols [4,7,8]. Bolstering the fear of their use as bioterrorism agents, several hemorrhagic fever viruses have a history of state-sponsor...

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Sequence analysis of the Ebola virus genome: organization, genetic elements, and comparison with the genome of Marburg virus

Cited by 288 publications

References 43 publications

Ebola virus: new insights into disease aetiopathology and possible therapeutic interventions

Ebola virus: new insights into disease aetiopathology and possible therapeutic interventions

Filovirus Replication and Transcription

Filovirus-like particles as vaccines and discovery tools

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