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Monkeypox virus genome

The poxvirus genome is about 200kb in size and encodes about 200 proteins. It is a linear double-stranded DNA genome with covalently closed hairpin ends (no free 3' or 5' ends). It contains 10kb inverted terminal repeats (ITR) at each end. Genes are closely packed: intergenic regions of more than 100bp are rare.

The central conserved region encodes "housekeeping" genes involved in transcription, replication and virion assembly. The genes encoded in the terminal regions vary between poxviruses and encode proteins involved in host range and pathogenesis. image


REFERENCE STRAINS
Monkeypox virus Nigeria/MPXV-M5312/2018
Sequence | Proteome
(ref changed from MT903344.1 to NC_063383, 02/06/2022)
Vaccinia virus strain Western Reserve
Sequence | Genome | Proteome
Variola virus India-1967
Sequence | Genome | Proteome


Gene naming: In 2021, a unified nomenclature for Orhtopoxvirus genes was proposed. Previously, genes for many viruses had been named differently. Vaccinia Copenhagen genes were named after the HindIII restriction enzyme digestion profile of vaccinia virus. The individual digestion fragments were named according to the size order A, B,..., O, P. Genes are numbered consecutively within each HindIII fragment and designated as right-handed (R) or left-handed (L) transcribed: Vaccinia Copenhagen and Monkeypox (MPV).

Genome evolution:
-The mutation rate of poxviruses is estimated to be between 10-5 and 10-6 mutations per replication site.
- Because these viruses infect immune cells, they are subject to cytoplasmic DNA editing by cellular enzymes such as APOBEC3, which can significantly increase the mutagenicity induced by viral DNA polymerase errors. (discussion)
-Poxviruses are able to evolve by homologous recombination between coinfecting strains . They can also acquire foreign genes by non-homologous recombination.

Important: Poxvirus genes are transcribed in the cytoplasm by viral enzymes and are not spliced because there are no splicing machinery outside the nucleus. If they were expressed from a plasmid in the nucleus, artefacts could result from mRNA splicing.
The surface proteins of mature virions are not expressed in the endoplasmic reticulum of the cell, and the disulfide bonds are made by a viral sulfohydryl-oxidase in the cytoplasm. Expression of these proteins from plasmids can lead to artefacts.

Sources:
Fundamentals of Molecular Virology, 2nd Edition; N. H. Acheson, Wiley ISBN: 978-0-470-90059-8
Monkeypox reference strain: Nextstrain, Richard Neher.