Structure/Genetics
The virions of both Marburg and Ebola viruses are pleomorphic, taking forms ranging from 14,000nm long filamentous particles to small spheres. The virion envelope is derived from the plasma membrane of host cells, and tightly encloses the genome-containing nucleocapsid. The surface of the envelope is studded with 10nm long glycoprotein peplomers that aid in viral entry into host cells. (click image for larger version) |
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All Filoviruses have a single-stranded, negative-sense RNA genome, approximately 19,000 base pairs in length. This genome is non-segmented, thus eliminating the possibility of segment recombination between different viral strains or species. The seven genes that exist in both Marburg and Ebola viruses are arranged sequentially along the length of the genome, with non-coding sequences at both the 3’ and 5’ ends that are thought to play a structural role in initiation of transcription and replication. Sequences indicating transcriptional start and termination sites are conserved between different filovirus species, however there is 37-41% sequence variation in the coding regions between the Ebola and Marburg species.
Key differences between the genetics of the Ebola and Marburg viruses exist in the organization of their glycoprotein (GP) genes. The Marburg virus GP gene encodes one product in one open reading frame, while the Ebola virus GP gene encodes two polypeptides in two open reading frames. The primary product of the Ebola GP gene is a small, secreted glycoprotein that gets released in large quantities from infected cells. The Marburg virus does not produce a similar secreted glycoprotein. SGP is found in large quantities in the serum of infected patients. Although its precise function is unclear, it is suspected to interfere with neutrophil function by binding to their surface Fc?3 receptors. Through similar interactions with other cell types, SPG may play a role in the inhibition of the inflammatory response.
The non-secreted form of the glycoprotein (GP) exists in both Marburg and Ebola viruses and is the major envelope-associated protein of filoviruses. The structure and chemistry of this protein has been extensively studied as it is a prime target for vaccine development. GP has both conserved and variable regions. The variable regions are the most heavily glycosilated with an extended structure, and are thus able to tolerate mutations easily.
A precursor form of GP, known as GP0, is differentially cleaved post-translationally by furin, creating two forms of GP, GP1 and GP2. GP1 and GP2 dimerize, and then the heterodimers form trimers that make up the virion surface spikes, or peplomers, which are critical for viral entry into host cells. GP has been implicated to have direct immunosuppressive and cytopathic effects, such as the inhibition of T-cells proliferation in response to mitogen. Other envelope proteins include VP40, which is suspected to facilitate budding by promoting interactions between newly formed nucleocapsids and the plasma membrane, and VP24, which does not have a defined function.
In addition to the envelope and secreted glycoproteins, the other major category of proteins of the filoviruses is the ribonucleocapsid complex. The major structural protein of this complex is nucleoprotein (NP). NP ranges in size from about 96-104kD in different filovirus species and plays an important function in binding genomic RNA. The other proteins of the ribonucleocapsid are polymerase, VP30, and VP35, all of which are involved in transcription and replication.
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This page last updated: 14 April 2004.
