Accordion genome mpox virus used to evolve, infect humans

Poxviruses have long been a source of fear and curiosity in humans. In the last century, smallpox, a notorious poxvirus alone, may have killed more than 500 million people.

Smallpox killed rich and poor, young and old, and killed one-third of those infected. Evidence of the efficacy of the smallpox vaccine provided a turning point. As a result, there is a concerted effort around the world to vaccinate and ultimately eradicate this terrible disease. This feat demonstrates the power of continued global public health measures.

Acne 15 minutes

Another poxvirus, MPOX, recently made headlines after a rapidly expanding global outbreak in 2022-2023. The virus was previously known as monkeypox in 1958, after a spill at a research facility involving monkeys; today, the name is considered erroneous and inappropriate: Since then, researchers have studied many cases in humans. MPOX has been discovered in sporadic outbreaks. They also found that multiple mpox lineages have circulated in humans, adapting through the accumulation of mutations primarily regulated by APOBEC proteins.

But it was not until 2022 that the disease became widely known due to outbreaks in more than 118 countries and the World Health Organization (WHO) quickly declaring it a public health emergency. The outbreak has infected nearly 100,000 people so far. According to the World Health Organization, the mortality rate from the infection is 1-10%.

The outbreak was caused by a clade called IIb (virus strains derived from a common ancestor) that resulted in very high rates of human-to-human transmission through close contact and sexual transmission. Although the rate of new infections has been declining, MPOX continues to spread among unvaccinated individuals worldwide. This increases the likelihood that a more virulent and contagious strain will emerge and become prevalent somewhere.

Expand and contract as needed

Mpox, like all poxviruses, are DNA viruses. The MPOX genome is approximately 197 kilobases (kb). The core gene is a gene that is closely conserved (i.e., retained during evolution) among various poxviruses, plus two approximately 6.4 kb long segments, each located at opposite ends of the genome. Researchers don’t yet know the function of these parts, but suspect they influence how well the poxvirus infects different hosts.

The MPOX genome also has a series of base sequences that repeat in a pattern, which researchers believe plays a role in viral evolution.

The mpox virus family is also thought to be able to escape selective evolutionary pressures. It does this by duplicating genes and/or accumulating mutations and significantly expanding its genome, or shrinking its genome by deleting gene segments or rendering them inactive. This rhythmic expansion and contraction is called the genomic accordion.

find accordion

A study published on April 18 showed nature communicationsResearchers at the Icahn School of Medicine in New York and multiple institutions in Spain conducted extensive sequencing of the genome of the 2022 outbreak of the MPOX virus. They used advanced genome sequencing technology to piece together the comprehensive genome of the MPOX virus from scratch.

They found that a 6.4 kb long portion of the virus strongly affects the virus’s human-to-human transmissibility. They also reported that variations in three genes in particular may influence the evolution of the virus. Importantly, a 6.4 kb long section that scientists had previously thought was not very informative was actually found to be the viral genome accordion.

All mpox genomes can be divided into two distinct but broad clades: I and II. Clade I is thought to have higher mortality. Each clade has subclades or lineages defined by specific evolutionary processes. The researchers also found evidence of significant differences in MPOX virulence in animal models. Like other similar studies, this new study further supports the idea that the 2022 outbreak mainly involves a new virus lineage, clade IIb, which is more suitable for human-to-human transmission than clade I or IIa.

Outbreak in the Democratic Republic of the Congo

Between September 2023 and February 2024, health workers discovered a large-scale mpox outbreak in the Democratic Republic of Congo (DRC), centered in a mining village and quickly spreading to multiple regions in the country. This outbreak is associated with greater transmission and mortality. Researchers quickly identified mpox clade I as the culprit.

This epidemic is different from previous epidemics, which were sporadic, independent spillover events that spread through person-to-person contact and affected young people rather than children. On April 14, researchers from Belgium, Canada, the Democratic Republic of Congo, France, Ghana, Nigeria, South Africa, and the United States uploaded a preprint paper describing the results obtained from 241 individuals suspected of being infected during the outbreak. Genomes of virus samples.

Genomic data suggest that distinct lineages of clade I are associated with human-to-human transmission. The researchers also found evidence in genome fragments that are very similar to viruses isolated and sequenced in recent years, proving that this lineage spread from recent zoonotic viruses.

One eye on the genome

As with any viral infection, without urgent intervention, the epidemic has the potential to spread rapidly across national and even continental borders and become another global epidemic.

To prevent this outcome, the genome sequence before and during the MPOX outbreak provides a clear understanding of the evolutionary dynamics of the virus, which it used to invent new ways to move and survive between different animal and human populations.

Therefore, through rigorous genomic research and coordinated public health efforts, we can mitigate emerging pathogens and threats to the world’s health security.

The author is Senior Advisor, Vishwanath Cancer Care Foundation and Adjunct Professor, Indian Institute of Technology, Kanpur. All opinions expressed are personal.