Will mpox go global again? Research shows that they evolve in strange ways

Will mpox go global again? Research shows that they evolve in strange ways

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Mpox virus particles (purple) appear to spread more easily between people.Credit: NIAID/SPL

As smallpox continues to spark localized outbreaks in Africa and, on occasion, in other parts of the world, researchers are racing to understand how the virus managed to spread globally in 2022 — and how it could do so again.

A study published in December found that the strain that caused an outbreak in 2022 persisted in the testicles of mice for weeks after infection and caused tissue damage.1Which highlights the possibility of the virus affecting men’s fertility. This has not yet been studied in humans.

The study has been published on the preprint server bioRxiv and has not yet been peer-reviewed. Meanwhile, the virus continues to evolve. In December, health officials reported the presence of a strain of HIV Combines the genetic elements of two existing species, or cladesfor the first time. Although it is normal for viruses like smallpox to evolve, the more opportunities they have to spread, the more likely they are to eventually evade protection from vaccines and treatments.

Together, these data show that “scientists still have a lot to learn” about existing strains, let alone new ones, says Bugoma Tetanji, an infectious disease physician at Emory University in Atlanta, Georgia. Smallpox belongs to the poxvirus family, which also includes smallpox, “so we should not underestimate what it can do if it is allowed to become firmly established in human populations and continue to adapt,” she adds.

Mbox is evolving

Smallpox infection can cause painful, fluid-filled lesions on the skin, fever, and, in severe cases, death. There are four known clades of mpoxvirus: branches Ia, Ib, IIa, and IIb (see “Quick guide to clades of mpoxvirus”).

The virus has been infecting humans since the 1970s. Historically, the disease rarely spreads widely, but that all changed in late 2010, when a type 2 strain caused a large outbreak in Nigeria. A similar type IIb strain sparked a global outbreak in 2022, in which more than 100,000 people were infected. And it’s still going on.

A quick guide to mpox virus interfaces

Clade Ia: This clade has spread through Central Africa since the virus was first discovered to infect humans in 1970. Most infections have been among children, and until the past few years, transmission occurred mainly from animals to humans.

Clade Ib: This clade has caused a rise in cases in Central Africa since its discovery in late 2023. It is known to spread from person to person, through means including sexual contact.

Branch IIa: The less-studied branch of the Mabox. It has spread mainly in Guinea, Liberia and Côte d’Ivoire. The routes of transmission are not fully understood; There is no documented evidence of sexual transmission, but all forms of close contact likely contribute to its spread.

Clade IIb: The clade responsible for the global outbreak in 2022 that is still simmering. It is known to spread from person to person, through means including sexual contact. The most affected population was men who have sex with men.

In 2025, there was a significant increase in infections with smallpox I, which has historically caused sporadic but deadly outbreaks in rural areas of central Africa. A new subtype I, called Ib, began spreading among people in dense urban areas in late 2023, possibly through sexual contact. This spread has scientists worried because the sudden appearance of clade Ib mpox reverses the trajectory of clade II before it became global, Titanji says.

Mpox disease spreads rapidly. Here are the questions researchers are racing to answer

For the past two years, researchers have been racing to understand how the two new MOCs, Ib and IIb, differ from their predecessors. Data from rodents infected with poxvirus provide evidence to support the theory that these organisms are less lethal but more adept at spreading from person to person because they cause milder disease.2.

Mice infected with branch Ib mpox had higher survival rates than those infected with branch Ia, yet they transmitted the same amount of infectious virus. The researchers found that the appearance of visible skin lesions was significantly delayed in cases of Clade Ib infection.

These findings help explain why the virus is “very effective at spreading through sex,” as people can inadvertently transmit the virus before they develop symptoms, Titanji says.

Fertility issues?

Another group of scientists studied how mice were infected with clade IIb mpox bacteria1. They found high levels of infectious virus in the rodents’ testes for at least three weeks after infection, suggesting that the male reproductive tract may serve as a reservoir for the virus, and helps explain why the virus is transmitted so efficiently through sexual intercourse.

The researchers found that the infection caused tissue damage leading to loss of sperm production.

“We were expecting to see some inflammation or dysregulation, but seeing the potential for this infection to impact male fertility was shocking,” says study co-author Alison Kelvin, a specialist in emerging viruses at the University of Calgary in Canada.

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