The Ebola virus and it’s close relative the Marburg virus are members of the Filoviridae family. These viruses are the causative agents of severe hemorrhagic fever, a disease with a fatality rate of up to 90% . The Ebola virus infects mainly the capillary endothelium and several types of immune cells. The symptoms of Ebola infection include maculopapular rash, petechiae, purpura, ecchymoses, dehydration and hematomas .
Since Ebola was first described in 1976, there have been several epidemics of this disease. Hundreds of people have died because of Ebola infections, mainly in Zaire, Sudan, Congo and Uganda . In addition, several fatalities have occurred because of accidents in laboratories working with the virus . Currently, a number of scientists claim that terrorists may use Ebola as a biological weapon [14, 16].
In the 3D model presented in this study, Ebola-encoded structures are shown in maroon, and structures from human cells are shown in grey. The Ebola model is based on X-ray analysis, NMR spectroscopy, and general virology data published in the last two decades. Some protein structures were predicted using computational biology techniques, such as molecular modeling.
The Ebola virion is rod-shaped or 6-shaped, is 80 nm in diameter and up to 1,400 nm in length . In comparison, the diameter of HIV is 100–120 nm [18,19]. In general, filoviruses are very large, and only mimiviruses and megaviruses are larger in size [20, 21]. Similar to many other human viruses, Ebola has a membrane envelope. This envelope is formed from the membrane of the host cell during virus budding. The viral particle also captures a number of human proteins (for example, components of the major histocompatibility complex or surface receptors) that, in some cases, may alter the infectivity of the virus [3,4]. The host proteins represented in the viral particle are not constant. Unfortunately, information on the Ebola virus is limited, and this virus has not been described as thoroughly as HIV or the influenza virus . The main Ebola surface protein, encoded by the gp gene, mediates entry of the virus into the host cell . The Ebola GP protein resembles the HIV GP protein and influenza hemagglutinin in terms of its structure and function. Ebola GP forms trimers, and each monomer contains a transmembrane and extracellular subunit [23,24,25]. The Ebola virus particle contains a matrix layer that is located under the viral membrane. This matrix layer, which is likely to have a spiral structure, contains VP40 . VP40 proteins interact with the viral membrane and with each other. The membrane interaction is mediated by the short C-terminal domain, and the relatively large N-terminal domain is responsible for binding VP40 proteins to each other . VP40 proteins form dimers that subsequently oligomerize into circular structures containing different numbers of units . VP40 is also the major protein involved in budding [36, 37]. The nucleocapsid of the Ebola virion is located in the very center of the particle and has a spiral structure. The nucleocapsid is formed mostly by the NP protein, which is responsible for the binding of viral RNA . The diameter of the helix is approximately 50 nm and contains an inner channel that is approximately 20 nm wide . The Ebola nucleocapsid shares a number of structural features with the nucleocapsid of the human respiratory syncytial virus [31,7]. The Ebola genome consists of single-stranded RNA, contains 7 genes and is slightly less than 19,000 nucleotides in length . There is one more component of nucleocapsid — protein VP24. Although the function of VP24 is not entirely clear, data indicate that this protein plays not only a structural role, but it also functions as an interferon antagonist [35, 26, 27]. The Ebola virion also contains RNA-dependent RNA polymerase (L protein) and minor proteins VP30 and VP35. Recent data indicate that these structures are likely to be located at one end of the filamentous particle . The L protein, which is responsible for reproduction of the viral genome, is the largest of the viral proteins (L is for “large”). VP30 is a transcription factor, and VP35 is an interferon antagonist and polymerase cofactor [8,9,10]. Enveloped viruses usually capture a number of host cell proteins from the cytoplasm during budding, and Ebola is no exception. Components of the host cytoskeleton are often found inside the virion . In the Ebola virus, the amount of captured cytoplasm varies, and this may affect the distribution of human proteins in the virion and the particle shape . Several important articles concerning filoviruses morphology were published after the Ebola model was complete. The published data shows that Ebola nucleocapsid contains 11 NP proteins per turn of the helix [38,39]. This information will be taken into account in the next versions of Ebola model.
- Project manager, 3D-visualizator, 3D-technologist, molecular modeller, designer
- Ivan Konstantinov
- Researcher, scientific advisor
- YuryStefanov (Ph. D)
- Alex Kovalevsky
- Molecular modeller, researcher, consultant
- Anastasya Bakulina (Ph. D)
- Kirill Grishanin
- We are grateful to Dr. Ronald Harty for useful comments and providing important information
- We also want to thank Dmitry Barbanel and Amy Gordon for their help in the preparation of the poster
Date: Feb 03, 2012
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