Mononegavirales

The Mononegavirales are an order of viruses comprising species that have a non-segmented, negative sense RNA genome. The order includes four families:

• Bornaviridae (Borna disease virus)
• Rhabdoviridae (e.g. Rabies virus)
• Filoviridae (eg Marburg virus, Ebola virus)
• Paramyxoviridae (eg Newcastle disease virus, measles virus)

A number of important human diseases, both established (mumps, measles, rabies) and emerging (ebola haemorrhagic fever, borna disease, Hendra virus, Nipah virus), are caused by viruses from this order.

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Structure

Virions possess an envelope and a helical nucleocapsid containing an RNA-dependent RNA polymerase (RDRP) and genomic RNA. The genome contains 6-10 genes, although a process known as RNA editing allows for a greater number of gene products.

Taxonomic Structure

Life cycle

Entry

Viral particles enter a cell by binding to a cell surface receptor (eg sialic acid) and inducing fusion between the viral envelope and the cell membrane. In the cytoplasm, the particle uncoats, releasing the genome.

mRNA synthesis

The genomic sequence is negative sense, therefore it does not code for proteins. Complementary sequences must first be transcribed by an RNA-dependent RNA polymerase (RDRP). This inability of the genome to produce proteins requires the virion to carry the RDRP with it into the cell. This is in contrast to positive strand viruses which can synthesise RDRP once inside the cell.

The RDRP released from the viral particle binds to the single promoter site at the 3' end of the genome and begins transcription. The RDRP pauses at the gap between each gene, releasing the completed mRNA. Transcription can then either terminate or continue transcribing the next gene. This creates a polarity of transcription, where genes close to the 3' end of the genome are transcribed in the greatest abundance, whilst those towards the 5' end are least likely to be transcribed, since the RDRP has more opportunities to terminate. By placing the genes in order of required abundance from most to least, the virus is able to use this polarity as a form of transcriptional regulation. As a consequence, most genomes begin with the gene for the nucleocapsid protein and end with the gene for the RDRP.

Protein synthesis and genome synthesis

Once mRNA production has begun, the cellular protein translation system is co-opted to produce viral proteins which accumulate in the cytoplasm. At some point, possibly determined by the concentration of nucleocapsid protein, the RDRP molecules transcribing the viral genome begin ignoring the gap sequences between genes and produce full-length, positive-strand antigenomes. These are in turn transcribed into negative strand viral genome copies.

Assembly and exit

The newly synthesised viral proteins and genomes self-assemble and accumulate near the inside of the cell membrane. The virions bud off from the cell, gaining an envelope from the cell membrane as they exit. The new viral particle infects another cell to repeat the cycle.

RNA editing

RNA editing is a mechanism used by some members of Mononegavirales to produce multiple proteins from a single gene. It occurs when the RDRP enzyme inserts extra residues into the mRNA being synthesised. This creates a frame-shift, altering the amino acid sequence encoded by the mRNA.

Evolution

As with other RNA viruses that do not have a DNA intermediate, members of Mononegavirales are able to evolve at a rapid rate due to the absence of proof-reading ability in the RDRP enzyme. A high mutation rate occurs in the production of new genomes (up to 1 per 1000 bases).

References

Büchen-Osmond, C. (2003). 01. Mononegavirales. In: ICTVdB - The Universal Virus Database, version 3. Retrieved April 6, 2004 from http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/index.htm

Dewhurst, S. (2003) University of Rochester Medical Center Department of Microbiology and Immunology Selected Virology Lecture Notes. Retrieved April 6, 2004 from http://www.urmc.rochester.edu/smd/mbi/grad2/pdf/gr03nns.pdf