The Mpox virus uses a ‘genomic accordion’ to evolve and infect humans (GS Paper 2, Issues relating to the development and management of Social Sector/Services)
Context
- Poxviruses have long been a cause of fear as well as curiosity for humankind. One particularly infamous poxvirus, smallpox, alone may have killed more than 500 million people in the last century.
Mpox’s 15 minutes
- Another poxvirus, mpox, was recently in the headlines after a rapidly expanding global outbreak in 2022-2023.
- The virus was previously called ‘monkeypox’ after a spillover event in a research facility involving monkeys in 1958; the name is considered both wrong and inappropriate today: since then, researchers have identified mpox in many sporadic outbreaks among humans.
- They have also found multiple mpox lineages have been circulating in humans, adapting by accumulating mutations modulated largely by the APOBEC proteins.
Apolipoprotein B Editing Complex (or APOBEC3)
- The interaction between the virus genome and an important family of proteins coded by the human genome is known as the Apolipoprotein B Editing Complex (or APOBEC3).
- These proteins offer protection against certain viral infections by editing the genome sequence of the virus while it replicates in the cell.
Outbreak
- It wasn’t until 2022 that the disease became widely known, thanks to outbreaks in more than 118 countries and the World Health Organisation (WHO) quickly declaring it a public health emergency.
- Based on WHO data, infections have a mortality rate of 1-10%.
- The outbreak was due to one clade (strains of the virus descended from a common ancestor) — called IIb having developed very high human-to-human transmission through close contact and spread through the sexual route.
- While the rate of new infections has been dropping, mpox continues to circulate among unvaccinated individuals worldwide.
- This increases the chance that a more virulent and transmissible strain might emerge and become endemic somewhere.
Expanding, contracting as required
- Mpox, like all poxviruses, are DNA viruses.
- The mpox genome also has a sequence of bases repeating in a pattern, which researchers believe play a role in the virus’s evolution.
- All mpox genomes can be divided into two distinct yet broad clades: I and II. Clade I is thought to have a higher mortality. Each clade has sub-clades, or lineages, defined by specific evolutionary processes.
- The mpox family of viruses is also known to be able to evade selective evolutionary pressures.
- It does this by duplicating genes and/or accumulating mutations and expanding its genome significantly or contracting its genome by deleting gene stretches or inactivating them.
- Such rhythmic expansions and contractions are called genomic accordions.
One eye on the genome
- As with any viral infection, without urgent intervention, the outbreak has the potential to spread rapidly across national, and even continental, boundaries and emerge as another global outbreak.
- To prevent such an outcome, genome sequences from before and during mpox outbreaks have provided well-lit glimpses of the evolutionary dynamics the virus uses to invent new ways to move between and survive in different populations of animals and people.
Conclusion
- Thus, through rigorous genomic investigations and coordinated public health efforts, we can mitigate the threat of emerging pathogens and the world’s health security.
