A patient showed a wound caused by MPox while confined in the isolation area of the Arzobispo Loayza Hospital in Lima, Peru, last August. In total, more than 90,000 people were infected. ERNESTO BENAVIDES (AFP)
On April 29, 2022, a British citizen developed a rash while traveling in Nigeria, Africa. After returning to the UK he decided to go to hospital as his rash worsened, his lymph nodes swelled and his fever rose. There they confirmed that it was monkeypox (or Mpoxen, as the World Health Organization (WHO) called it). It is a disease of zoonotic origin, caused by a virus that occasionally originates from some animals and which, until then, was difficult to transmit from person to person. But in just a month there were thousands of cases in Spain, Portugal, the United States, Colombia, Singapore… The WHO was forced to declare an international health emergency. Now, senior virologists have discovered that the strain that caused the outbreak has been circulating among humans for several years. They also demonstrated that a human enzyme with antiviral activity would have accelerated the pathogen’s mutation rate, worrying scientists who fear MPox will remain with us.
Today the threat of the virus is less. Although there are still new infections, the WHO withdrew its warning over the summer. But the pathogen is still there and it is still unknown where it came from. In the past, outbreaks have always had the same characteristics: a transition from animal to human, usually a rodent (its best-known reservoir) or a monkey, followed by some infections between humans. The virus did not adapt well to the human environment. But something must have changed in 2022, when thousands of people became infected within a few months (at the end of October 2023 there were already more than 91,000 people). Most had never traveled to countries where MPox is endemic, such as Nigeria or the Democratic Republic of Congo, so there was sustained human-to-human transmission over time, not consistent with a zoonotic disease.
Now a large and renowned group of scientists, including some of those who first characterized SARS-Cov-2 after the coronavirus pandemic, have sequenced the genome of almost a hundred samples of the virus, some of which date back to the 60s last century. They wanted to know where and when the lineage called B.1 that caused the 2022 outbreak emerged. These Mpoxen are divided into the so-called clade IIb, whose origin lies in the West African region. Fortunately, its lethality is ten times lower than that of class II viruses endemic to the center of the African continent.
The results of this research, published today in the prestigious journal Science, suggest that the 2022 samples are not the first of the outbreak: they have up to 42 mutations in their DNA, the tracing of which leads them to a case from 2015. which already had one of these changes. The following year, Nigerian authorities reported a few cases of Mpoxene in humans, but at the time they were thought to be of zoonotic origin, jumping from animals and unrelated. They were wrong. Back then, in 2016, the researchers came to the conclusion in their work that “the virus circulated sustainably among people.”
“It is unclear what led to the global spread of B.1. There doesn’t appear to be anything special about this virus in this lineage.
Áine O’Toole, virologist at the University of Edinburgh (UK)
To support this conclusion, they rely on the origin of these 42 changes in viral DNA. They focused on nucleotides, the four basic elements of DNA known by the letters A, T, G and C. They then confirmed that virtually all of these mutations were linked to the action of an enzyme, APOBEC3. Rodents, the alleged reservoirs of the virus, are found in almost all mammals and have only one copy, which they express in the spleen and bone marrow, but not in other tissues. In humans it is part of the immune system. Its job is to remove parts of the virus’s DNA that make it difficult to replicate. In all cases from 2017 onwards, these genetic changes occur, which would rule out that the changes occurred before the virus jumped from animals to humans.
The lead author of the research, virologist from the University of Edinburgh (UK), Áine O’Toole, says: “Since the spread to the human population (we estimate this was the case at least in 2016), the traces have been The edition of APOBEC3 are seen as scars in the viral genome.” When these viruses begin replicating, they expose their DNA, an opportunity that this enzyme takes advantage of to swap some letters for others. In most cases, this disrupts its replication machinery, but in other cases the pathogen manages to replicate already with the APOBEC3 mark. What O’Toole doesn’t have an answer to is the timing of the outbreak. Why did it erupt in May 2022 even though it had already been around for at least six years? “It is unclear what led to the global spread of B.1. There doesn’t seem to be anything special about this virus, this lineage; Most likely it had the opportunity to spread widely because it penetrated certain population networks.”
Antonio Alcamí, virologist at the Severo Ochoa Molecular Biology Center (CMB/CSIC), emphasizes the importance of knowing when it started circulating: “It was thought to be new, but since 2016 and in humans the virus has the same. “ brand than that of the 2022 outbreak. For Alcamí, who has nothing to do with the work published in Science, his findings are very relevant. “It was thought that MPox had not adapted to humans, but if we now see that it has been infecting humans for years, that would be a warning that it is adapting to humans.”
“The longer it circulates among people, the greater the likelihood that the virus will become more humane”
Raúl Rivas, Professor of Microbiology and Genetics at the University of Salamanca
One of the keys may be that APOBEC3 accelerated the virus’s mutation rate. Based on what was known from other orthopoxviruses such as human smallpox and previous samples, the rate of change in Mpoxes was very low. However, there were 42 changes in its DNA in two or three years, a rate 28 times faster in the B.1 lineage than the previous ones. “The key here is to know whether these mutations influence greater transmissibility between people,” emphasizes the professor of microbiology and genetics at the University of Salamanca, Raúl Rivas, who also highlights the dating of the first cases with these mutations: “The more “ The longer it circulates among people, the greater the chance that the virus will become more humane.”
The authors clarify and the experts interviewed confirm that the fact that this antiviral enzyme is behind the mutations present in the B.1 lineage does not mean that APOBEC3 increases the virus’s ability to replicate and transmit between people. The professor at the University of Valencia, who studies phylogenomics and evolution of viruses, emphasizes this: “APOBEC3 is not the cause, but it is mutagenic and among the mutations that have occurred, some have allowed greater transmissibility of the virus.” What remains to be done remains is to connect the antiviral enzyme with this greater infectious capacity. And that is something that is urgent.
In their conclusions, the study authors suggest that it would represent a paradigm shift if a link between APOBEC3 and the long-term persistence of Mpoxen in humans were found. Oriol Mitjà from the Germans Trias i Pujol Hospital in Barcelona agrees and was involved in the discovery of a fulminant form of monkeypox in people with advanced HIV infection. “There will be new outbreaks of zoonotic diseases in the future, but if this transmission between humans continues, we could say that it is already a human virus.” It is like it was the case with HIV [también zoonótico inicialmente]a paradigm shift,” he adds.
For the experts interviewed, the findings now only increase the concerns that have existed since this Briton was diagnosed. The vast majority of the more than 91,000 people infected so far are under 50 years old. That is, they were not vaccinated against smallpox, which was eradicated from the earth in 1980. There is a risk that smallpox will occupy the niche of its viral relative and do so in an unvaccinated population. It could be worse. If the B.1 lineage manages to spread from person to person, it could also transmit clade I viruses, which kill 10 out of 100 infected people.
You can follow THEME on Facebook, X and Instagram, or sign up here to receive our weekly newsletter.
Subscribe to continue reading
Read without limits
_