Scientists Warn of Rapidly Diverging Mpox Strains Driven by Recombinant Events and Evolution

Medical News: In an alarming revelation, scientists have observed an unusual phenomenon with Mpox (previously known as monkeypox) virus clade 1b, which is responsible for the latest outbreak. Researchers from Auxergen Inc. in Baltimore, USA; Auxergen Srl at Tecnopolis Science and Technology Park, Italy; Kaohsiung Municipal United Hospital, Taiwan; and Kaohsiung City Government Health Bureau, Taiwan, have discovered that this viral strain is diverging at an unexpectedly rapid pace. This divergence, driven by genetic recombination and mutation, may complicate efforts to contain the spread and develop effective treatments.


Scientists Warn of Rapidly Diverging Mpox Strains Driven by Recombinant Events and Evolution

As of August 2024, the Mpox outbreak was declared a Public Health Emergency of International Concern due to the virus’s high transmission rate. The outbreak, already affecting over 18,700 people and leading to more than 500 deaths across 14 countries, shows worrying signs of underreporting. This Medical News report dives into the reasons why this outbreak is particularly challenging, especially with the rapid divergence of Mpox clade 1b.
 
Understanding the Rapid Evolution of Mpox Clade 1b
At the core of this evolution lies the genetic makeup of clade 1b, which has been undergoing what scientists refer to as “recombinant events.” Recombinant events occur when viral genomes mix and match genetic material, resulting in new viral strains that may have different behaviors, infection capabilities, or resistance to immune responses. In the past 11 months, researchers have observed a dramatic increase in recombinant clusters within Mpox clade 1b, with more than ten distinct recombination clusters identified in samples from various global regions, including the Democratic Republic of Congo, Thailand, Sweden, Kenya, and Uganda.
 
These recombination events are unusual compared to the previously dominant Mpox clade 2b, which was responsible for a major outbreak in 2022. While clade 2b showed limited recombination and mutation rates, clade 1b appears to have taken a far more aggressive path. The recombination rate of clade 1b is nearly 78 times higher than that of clade 2b during the initial outbreak periods, suggesting a higher rate of genetic shifts within infected populations.
 
The Influence of APOBEC3 and Genetic Mutation
A significant driver behind this rapid evolution may be the influence of the APOBEC3 gene mutation. APOBEC3 is an enzyme found in humans that typically targets viral DNA, causing mutations that hinder virus replication. However, with clade 1b, scientists believe the mutation may be aiding the virus's genetic shifts, allowing it to adapt rapidly in response to immune defenses or other environmental pressures.
 
The research team examined 32 Mpox clade 1b sequences from October 2023 to August 2024, collected in collaboration with the Global Initiative on Sharing All Influenza Data (GISAID). Phylogenetic analyses revealed that clade 1b has diverged into four distinct lineages and numero us subgroups, with 14 identified based on unique tandem repeat polymorphisms in its genetic sequence. In comparison, clade 2b only developed 11 subgroups during the 2022 outbreak, highlighting the higher mutation frequency of clade 1b.
 
Recombinant Clusters: A Growing Challenge
Within clade 1b, ten major recombinant clusters have emerged in under a year. These clusters indicate points where the virus’s genome recombines, which can lead to new genetic variants. The notable clusters include DRC IRB010, Thailand NIC31, Sweden PHAS11304, and multiple clusters from the Democratic Republic of Congo, Uganda, and Kenya.
 
The prevalence of these recombinant clusters suggests that superinfection events - when a host is infected by multiple viral strains - are likely frequent, increasing the chance of genetic recombination. This superinfection may also explain the rapid development of variant subgroups within clade 1b. Researchers noted that these recombinant events were detectable as early as October 2023, demonstrating that Mpox clade 1b has quickly diversified since it first began to spread.
 
Implications for Public Health and Control Measures
The rapid divergence of clade 1b raises several concerns for public health officials. With more recombination and higher mutation rates, there is a possibility that the virus could evade immune responses from prior infection or vaccination, potentially reducing the efficacy of existing treatments and preventive measures. In particular, the study’s findings indicate that current genomic surveillance efforts might need to intensify to keep pace with the virus’s evolution.
 
An additional challenge is the lack of sufficient clade 1b genetic sequences from affected countries. Researchers highlighted that limited laboratory capacity and testing infrastructure in countries like the Democratic Republic of Congo hinder comprehensive genetic analysis, potentially leading to an underestimation of the virus’s actual mutation and recombination rates. This scarcity of data complicates efforts to monitor and control the virus, as each new recombinant strain could carry unknown properties or resistance factors.
 
Potential Strategies for Improved Surveillance
Experts from the study urge a globally coordinated effort in genomic surveillance to track the virus’s genetic changes closely. Enhanced transparency in sharing Mpox genetic data would allow scientists worldwide to monitor the virus’s behavior and adaptation patterns, aiding in the development of targeted response strategies. By implementing robust sequencing practices and maintaining a transparent data-sharing network, health authorities could get ahead of new variants, identifying potential risks early and adjusting interventions accordingly.
 
Conclusion: The Urgent Need for Action
The rapid evolution of Mpox clade 1b underscores the critical need for timely and effective public health interventions. With the virus mutating and recombining at a pace previously unseen in Mpox outbreaks, researchers fear that further delays in addressing this evolution could lead to larger and more complex outbreaks. Health organizations must prioritize comprehensive genome sequencing and data sharing to better understand and predict how these new recombinant strains will impact the global response to the disease.
 
While it remains uncertain whether clade 1b will continue to diverge at its current pace, the findings highlight the importance of agility in public health strategies. Researchers emphasize that without urgent intervention and improved global collaboration, Mpox could potentially evade current containment efforts, complicating the path to controlling the outbreak and safeguarding public health.
 
The study findings were published in the peer-reviewed journal: The Lancet Microbe.
https://www.sciencedirect.com/science/article/pii/S2666524724002854
 
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