News Excerpt:

A poxvirus, mpox, was recently in the news after a rapidly expanding global outbreak in 2022-2023.

Background:

• 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.
• Smallpox didn’t discriminate between rich, poor, young, and old and killed a third of the individuals whom it infected.
• The turning point came with evidence of the efficacy of the smallpox vaccine.

About Mpox virus:

• Mpox, like all poxviruses, are DNA viruses. 
• The mpox genome has about 197 kilobases (kb).
• The virus was previously called ‘monkeypox’ after a spillover event in a research facility involving monkeys in 1958.
• Since then, researchers have identified mpox in many sporadic outbreaks among humans. 
• The mpox genome has a sequence of bases repeating in a pattern, which researchers believe play a role in the virus’s evolution.
• Researchers have found multiple mpox lineages have been circulating in humans, adapting by accumulating mutations modulated largely by the APOBEC proteins.
• The mpox family of viruses is 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.
• Since 2022, the disease became widely known, due to its outbreaks in more than 118 countries.
• The World Health Organisation (WHO) has declared it a public health emergency. 
• The outbreak was due to one clade - 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.
• Till date, this outbreak has infected almost 100,000 people. Based on WHO data, infections have a mortality rate of 1-10%.

Key highlights of the study on mpox virus:

• Researchers at the Icahn School of Medicine in New York and multiple institutions in Spain extensively sequenced the genome of the mpox virus implicated in the 2022 outbreak. 
• They used advanced genome sequencing technologies to piece together a comprehensive genome of the mpox virus from scratch.
• They found that the 6.4-kb-long sections of the virus strongly influenced the virus’s human-to-human transmissibility.
• Importantly, 6.4-kb-long sections, which scientists had previously considered to be not so informative, were actually found to be the virus’s genomic accordions.
• They also reported that variations in three genes in particular could affect the virus’s evolution. 
• All mpox genomes can be divided into two distinct yet broad clades: I and II. 
• Clade I has a higher mortality. 
• Each clade has sub-clades, or lineages, defined by specific evolutionary processes. 
• Researchers have found evidence of significantly different mpox virulence in animal models. 
• The new study furthered the idea that the 2022 outbreak largely involved a new lineage of the virus, clade IIb, that was even better adapted to human-to-human transmission than clades I or IIa.

The outbreak in the Democratic Republic of the Congo (DRC):

• Between September 2023 and February 2024, health workers detected a large mpox outbreak detected in the Democratic Republic of the Congo (DRC), centred on a mining village and quickly spreading to a number of regions within the country. 
• This outbreak was associated with a significantly larger spread as well as mortality. Researchers soon confirmed mpox clade I was responsible.
• This outbreak differed from earlier ones, which were sporadic and self-contained spillover events, by spreading through human-to-human contact and affecting young adults rather than children. 
• The genomic data suggests a distinct lineage of clade I being associated with human-to-human transmission. 
• The researchers also found evidence that this lineage emerged from a very recent zoonotic spillover.

Way forward:

• 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.
• Thus, through rigorous genomic investigations and coordinated public health efforts, we can mitigate the threat of emerging pathogens and the world’s health security.