7. Mpox Virus Genome
One of the largest viral genomes, the Mpox genome is a gigantic 197 kb
single linear dsDNA molecule [5]. A collection of brief tandem
repeats 36, terminal hairpin loops37, and identical but oppositely oriented terminal
reads of around 6 kbp are present at every end of the genome. About 190
non-overlapping open-reading frames (>180 bp long), each
containing 60 or perhaps more amino acid residues, make up the genome.
The inverted terminal repeats exhibit four of these19. Mpox virus DNA contains only around 31.1% guanine
and cytosine 38. Mpox virus has two separate genetic
clades, the West African (WA) clade as well as the Central African (CA)
clade 39.
It consists of inverted terminal repeats (ITR) of 10kb at either end(Figure 2) . Genes are densely packed; intergenic areas longer
than 100bp are uncommon. The center conserved area contains genes that
perform ”housekeeping” functions like transcription, replication, and
virion assembly. The genes expressed in the terminal sections of
poxviruses differ from one another and encode proteins implicated in
host range and pathogenicity40. Deep sequencing
technology advancements have offered important insights into the
standing nucleotide variation (SNV) inherent in poxvirus populations.
These variants were previously unappreciated but are now recognised as
major contributions to poxvirus evolution. Furthermore, there is an
increasing knowledge of the role that genomic architectural alterations
play in determining poxvirus evolution. Key drivers of genomic
architectural alterations in poxviruses have been identified as
homologous and nonhomologous recombination, gene duplications, gene
loss, and horizontal gene transfer. A recent study 26found a higher-than-expected incidence of SNV accumulation in recent
samples of monkeypox virus . seven SNVs have been seen since the initial
epidemic in March 2022, with a total of 50 SNVs discovered since 2018.
The increased rate of SNV acquisition in recent monkeypox virus isolates
may be due to host adaptability, effective population size, and
selection coefficient. Selective sweeps or bottlenecks within
individuals or during transmission may limit accumulated diversity,
leading to disparities between epidemiological isolates and phylogenetic
data. The intergenic region (ITR) of monkeypox viruses has been observed
to expand or decrease, with varying clades having varying ITR lengths.
Variants in the Z-encoding region of the virus, such as the E3L gene,
have been found, potentially affecting PKR. Microsatellite variants,
particularly the A26 ortholog, contribute to genetic variability and
influence virus-host interactions. Overall, the data highlights the
complexities of poxvirus evolution and the various pathways involved in
producing genetic variation within poxvirus populations.