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Scientists comment on a UK Health Security Agency (UKHSA) announcement that a new mpox strain has been identified in England.
Dr Jonas Albarnaz, Institute Fellow, Capripoxvirus Biology, Pirbright Institute, said:
“The detection of a new recombinant mpox in the UK with genetic elements of both clade IIb and clade Ib is concerning because this shows that the continued global circulation of mpox since 2022 is enabling the virus to evolve in the human population. Clade IIb virus was responsible for the international mpox outbreak in 2022 that subsided in Western countries but did not stop to circulate entirely. Clade Ib emerged in the Democratic Republic of Congo (DRC) in 2023 and quickly spread to other neighbouring countries in Africa, and spread outside Africa in 2024, via international travel including to the UK. There was no evidence that clade Ib established community circulation outside Africa. This changed recently with the identification of clade Ib mpox in the US, Spain, Italy, the Netherlands, and Portugal in individuals without travel history, suggesting that clade Ib also circulates locally, albeit in small numbers, in these countries.
“Both clade Ib and IIb have patterns of mutations that indicate these viruses evolved during sustained human-to-human transmission. The identification of a new recombinant between Ib and IIb shows recombination might also contribute to mpox virus evolution. Recombination occurs when two related viruses infect the same cell (‘co-infection’) and exchange bits of their genetic material, generating a recombinant that combines properties of both co-infecting viruses. Co-infections are rare, but poxviruses, the group that include mpox, are known to be prone to recombination. If community transmission ensues, co-circulation of clade Ib and IIb will increase the chances of co-infections with both clades, which is a pre-requisite for recombination.
“From just one case it is impossible to gather much information about this new recombinant. However, its detection highlights the importance of continued genomic surveillance to detect new mpox variants early on. Clade I virus is associated with a more severe disease and higher mortality rates than the clade II virus, but we do not know if this recombinant transmits or cause disease differently either Ib or IIb.
Dr Jake Dunning, Consultant in Infectious Diseases and Senior Research Fellow at the Pandemic Sciences Institute, University of Oxford, said:
“Poxviruses have a known ability to recombine – that is, form a new genetic ‘hybrid’ when two different ‘strains’ of the virus infect the same human or animal cells and share their DNA. The emergence of recombinant monkeypox viruses containing segments of DNA from clade I and clade II monkeypox viruses, which are two, diverged, genetically distinct clades of virus, was always thought to be possible, with the likelihood thought to increase when clade I and clade II viruses co-circulate in the same geographical location.
“Recombination events can occur in animal cells (more likely in areas that have animal reservoirs of monkeypox) or in human cells. If this recombinant was formed in human cells, then the person will have been infected with both clades simultaneously (or in this case, the specific sub-clades Ib and IIb, which have been detected in multiple countries, including countries outside Africa).
“Exposure to the two different viruses may not have been simultaneous, but for a monkeypox virus infection in someone with a fully-functioning immune system, I think conditions favouring recombination would be optimal if the exposures to the two viruses were simultaneous or close together, before more the body’s immune responses to infection take hold and limit virus replication. Epidemiological investigations, including establishing the individual’s potential exposure histories and contact histories, confidentially, may also help public health officials understand more about how the infection was acquired and where further investigations and any necessary public health measures need to be focussed.
“The content of the UKHSA statement suggests, but does not confirm, that this infection may have been acquired through sexual transmission. Similarly, it raises the question about whether the recombinant virus was acquired in, or the recombination event occurred in. We do not know where the individual acquired the infection, or whether the recombinant formed in the affected individual or they were exposed to and became infected with the recombinant virus; hopefully more investigations can follow and more information can be shared in due course.
“A look-back sequencing exercise, particularly of viruses detected in areas or in contacts with which the affected individual has links, could help work out if this recombinant virus has been circulating for some time and was picked up by the individual. It’s certainly a call to keep watch for recombinant virus going forwards, by maintaining virus sequencing efforts. The virology work done to date by UKHSA and the University of Edinburgh, reported on Virologic.org*, confirms that the recombinant virus can replicate in cells; this is not surprising, given the vesicle swab sample came from someone with mpox symptoms.
“Since 2022 some experts have been predicting that a recombinant monkeypox virus will emerge, because of the large number of human mpox cases globally, but it should be a reminder to all countries that monkeypox viruses continue to evolve, and that mpox remains a global health problem, not just a problem confined to a particular country or region. Investigation of cases and genetic analyses of representative viruses remain important objectives globally.
“We also need studies to understand how common this recombinant virus is, and what the characteristics are of this genetic hybrid; for example, does it transmit in the same way and does it cause similar illnesses to those seen with mpox caused by clade Ib and clade IIb virus infections, which thankfully are mild and self-limiting in the majority? The hope – and it’s a reasonable expectation – is that a recombinant virus will not transmit as efficiently as the individual ‘component’ viruses, but we need laboratory data, case data, and epidemiological data to confirm that. It’s also a reasonable assumption that existing vaccinia-based vaccines will provide similar levels of protection against the recombinant virus as they do against clade I and II viruses, but again, some scientific work needs to be done to explore this further, even if just laboratory tests at this stage.
“There’s no need to panic, but countries do need to be aware of this finding and be on the lookout for more examples of recombinant virus infection, which will require specific efforts and activities, and do the necessary scientific and public health investigations if/when more cases occur, so that we can understand whether this is a significant event or not.”
Prof Geoffrey Smith FRS FMedSci, Professor, Sir William Dunn School of Pathology, University of Oxford, said:
“It has been known for more than 50 years that the genomes of closely related poxviruses can recombine to produce hybrid or recombinant viruses. But for this to happen, the same cell has to be infected with both parent viruses at the same time and it is inside the infected cell that recombination takes place to form the hybrid virus. Therefore, this is a rare event.
“It is made rarer still by the mechanisms orthopoxviruses deploy to prevent a second infection of a cell that is already infected by another orthopoxvirus. Therefore, to infect a cell with both viruses, the infection with each virus has to be at a very similar time, meaning within just a few hours. Consequently, to form this recombinant virus, it is likely that either both viruses were transmitted from the same source simultaneously, or that there were two transmission events at a similar time, each transmitting one virus. DNA sequencing might indicate if the patient with this new strain of monkeypox virus (MPXV) has only one strain of MPXV, which might indicate the preformed recombinant virus was transmitted to the patient. Or, if there is evidence of both clade 1b and clade 2b viruses within the same patient, the recombinant virus might have arisen with the patient.
“It will be interested to know which parts of the genome of the recombinant virus have derived from clade 1b and clade 2b MPXVs. The severity of disease, mpox, caused by this new virus might reflect where the majority of the genome originates. Clade Ib MPXV gives more severe mpox than Clade 2b MPXV, but both can be serious, especially if the patient is immunosuppressed, due to, for instance, HIV infection.”
Prof Trudie Lang, Director of the Global Health Network, University of Oxford, said:
It is of concern that there is an mpox case in the UK, and of further concern that it is a new recombinant mpox virus. This case highlights that mpox is circulating globally and is evolving, as predictable with these viruses. The recent experience we have had, and still persists in Africa, when clade Ib emerged, showed that this virus can cause severe disease, and so measures to reduce transmission and prevent spread are vital. In the UK we have excellent systems to identify cases, control onward infection, and implement vaccination campaigns as needed, and these measures should rapidly control this situation in the UK. Elsewhere in the world, in more vulnerable populations and where case detection and access to vaccinations is not so assured, this is harder to achieve. In terms of what we know about this recombinant, we will need to learn more about the nature and presentation of the infection to understand whether the disease characteristics have changed with this new recombinant. With clade Ib we observed changes in transmission, seeing person-to-person close contact as well as sexual transmission, changing from previous strains being limited mainly to animal-to-human and within households, and the previous European outbreak where the transmission was limited to close sexual transmission. So, if further cases of this strain appear in the UK, and anywhere in the world, it will be important to understand the route of transmission, the presentation and severity of disease, so we can assess whether this strain is more or less dangerous than previous ones and response accordingly with a connected global effort.
Dr Boghuma Titanji, Assistant Professor of Medicine, Emory University, said:
“The identification of a recombinant mpox strain containing elements of both Clade I and Clade II is precisely what experts in the field feared would happen if the virus continued to spread globally without a decisive response to stop it. Orthopoxviruses are well known for their ability to exchange portions of their genome and recombine to generate new variants, this is a core mechanism of their evolution. The key concern now is whether events like this will alter the virus’s transmissibility or virulence. There are also implications for how well existing testing platforms can identify these emerging recombinant strains. The more mpox circulation we permit, the more opportunities the virus has to recombine and adapt, further entrenching mpox virus as a human pathogen that is not going away.”
Declared interests
Dr Boghuma Titanji: I have no conflicts of interest.
Prof Trudie Lang: No conflict of interest.
Prof Geoffrey Smith: “I declare I have no conflicts of interest in making the above statement”
Dr Jake Dunning: “I was a member of two WHO Emergency Committees for mpox (2022-23; 2024-25). I am a member of UKHSA’s Technical Advisory Group for mpox. I conduct grant-funded studies on mpox in the UK and in Africa. I have no financial conflicts of interest to declare.”
Dr Jonas Albarnaz: “No conflict of interests to declare.”