-20 Ebola is a filamentous virus with a single-stranded RNA genome.
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- Ebola is a filamentous, single-stranded RNA virus with an unusual, variable-length, branched morphology. The helical capsid is enclosed inside a membrane.
- The mechanism of attachment and entry into the cell is unknown. Once inside, the viral RNA polymerase (L protein) begins to copy the (-) strand RNA to make (+) strand transcripts that mimic the structure of mRNA and are translated by host ribosomes.
- The rest of the replicative cycle is unclear, but probably involves assembly of the viral RNA at the host membrane and budding of the helical virus from the cell.
Ebola virus is difficult to study due to the high risk for the researcher, but plausible ideas about how the virus functions have been developed. The structure of this filovirus is large and unique. Ebola virus forms variable length filamentous capsids that are sometimes branched. Figure 19-28 shows an electron micrograph of Ebola virus. Only Ebola viruses of a certain size are infective and the virsuses variable length and large size is very unusual. It is possible that the very large variants are due to errors in assembly.
Figure 19.28. Ebola virus. An electron micrograph of Ebola virus. Note the variable length of the capsid and the branching that is sometimes seen. Some viruses are as long as 14,000 nm, though infective particles need only be around 970 nm long. (Source: Centers for Disease Control and Prevention)
The capsid has a helical morphology and is encased inside a membrane envelope. Several viral proteins and glycoproteins stud the membrane. One surface protein is extensively glycosylated and this may inhibit the generation of antibodies against the protein. VP30 in the matrix of the virus seems to be important during budding of the virus from the membrane. The primary capsid protein is a nucleoprotein (NP) whose N terminal interacts with viral RNA and the rest contacts other viral proteins in the matrix or envelope. These latter contacts may be important in viral assembly. Associated with the viral RNA is the L protein that is responsible for replication of the virus upon infection.
The nucleic acid of the virus consists of a single-stranded (-) RNA molecule, reminiscent of influenza virus. The genome codes for seven genes and seven separate transcriptional units are made into mRNA upon infection. Caps and polyadenylated tails are added during creation of the mRNA. The genome of Ebola is shown in Figure 19-29.
Figure 19.29. The genome of Ebola virus. The (-) ssRNA genome of Ebola virus is arranged in 7 separate units. The location of the coding region for each protein in shown in lower panel.
The mechanisms of attachment and entry of the virus are not clear, but are assumed to be similar to those of other (-) strand RNA viruses, such as influenza virus. Replication is thought to occur in the cytoplasm. An unusual feature of the transcription and translation of the Ebola genes is the fact that the GP protein is only expressed through transcriptional editing. In this process, the polymerase actually changes the growing mRNA, adding an extra A in the transcript to get the correct protein coding sequence for the GP protein. As remarkable as this is, such an "appropriate mis-processing" of genetic information at the mRNA synthesis level occurs in a variety of eukaryotes at very specific sequences. The primary product of the GP gene is called SGP and results from the non-edited mRNA. It is a smaller, non-structural protein that is excreted from the cell in large quantities. SGP may play a role in confounding the immune system and preventing the marshaling of an effective immune response.
The replicative cycle of the virus is unknown, but likely involves a mechanism where the membrane proteins are produced at the ER, processed through typical cellular pathways, and sent to the membrane. The viral polymerase makes further mRNA transcripts and eventually begins replication of the virus, first making (+) RNA strands and then (-) RNA. Eventually, enough viral proteins and (-) RNA accumulate to allow viral assembly and then budding of the virus through the membrane. The mechanism of viral assembly and budding is yet to be elucidated.[Prev] | [Next]