Research: Genomic changes associated with transmissibility of the monkeypox virus

Biopreparedness and virological surveillance involves studying the causes that favor zoonotic spillover and facilitates human-to-human transmission.

Scientists from Mount Sinai and the Carlos III Health Institute (ISCIII) in Madrid, Spain have worked together to detect and identify variations in the monkeypox viral genome that may be related to shifts in the virus’s transmissibility that were seen in the 2022 epidemic.

The results were released in the journal Nature Communications.

A double-stranded DNA virus that may infect both people and animals is called the monkeypox virus (MPXV). Fever, enlarged lymph nodes, and rash are among the symptoms of the mpox illness, which is caused by MPXV. The majority of mpox cases are moderate and resolve on their own, but they can be quite painful and leave lasting scars. during its discovery in 1958 in macaque monkeys that ate crabs and were sent to Belgium, MPXV has sometimes caused epidemics of human illness in Central and Western Africa during the 1970s. A growing number of MPXV infections and related illnesses were reported in May 2022 in many nations, including the US. These reports included clusters of cases that may have been connected to super-spreading occurrences in Belgium, Spain, and the UK. Even though there have been fewer new cases linked to the 2022 spillover over time, instances of the illness are still happening among people who have not received the vaccination, with an upsurge in cases reported in Central Africa as a result of a recent spillover. The likelihood of a more transmissible viral variation emerging and becoming endemic in the human population rises with the virus’s circulation among people.

Biopreparedness and virological surveillance involves studying the causes that favor zoonotic spillover and facilitates human-to-human transmission. When we observe significant changes in basic epidemiological features of a viral agent like monkeypox, it should reinvigorate our interest in understanding those transmission conditions. The increasing number of cases currently happening in Africa, and the 2022 epidemic, should be clear alert signals.

Gustavo Palacios, PhD

To conduct the investigation, scientists examined samples from 46 MPXV-infected individuals whose diagnosis and sequencing were completed at the ISCIII at the start of the 2022 mpox epidemic. The whole monkeypox viral genome of each research participant was sequenced at a high-quality level by the team to look for potential correlations between genomic changes in the various sequence groups and epidemiological connections related to the virus’s capacity to spread, mutate, and infect.

The study team found that regions of the genome that could be connected to viral adaptability were home to frequently detected genomic alterations. The paths of entry and exit, adaptation, and the viral replication cycle would all be influenced by those particular sites. These changes occur in low-complexity genomic regions, which are very challenging to sequence and examine, which explains why their previous neglect was warranted. Two cutting-edge sequencing technologies—deep short sequencing reads for accuracy and depth, and single-molecule long-read sequencing for covering highly repetitive regions made this very complex whole genome sequencing possible.

Researchers offer a tenable explanation for the increased transmissibility seen during the 2022 mpox epidemic by describing the genomic changes inside these repetitive genomic segments and connecting them to essential viral activities.

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These findings might be offering the first hints to help us understand the unique features of the strains associated with sustained human-to-human transmission, which has not ever been observed in these agents,

Better understanding of the doors that facilitate transmission of viral agents and impact their clinical presentations will enable us to develop more effective prevention and treatment strategies.

Dr. Palacios

Source: Mount Sinai Hospital Newsroom

Journal Reference: Monzón, Sara, et al. “Monkeypox Virus Genomic Accordion Strategies.” Nature Communications, vol. 15, no. 1, 2024, pp. 1-18, https://doi.org/10.1038/s41467-024-46949-7.


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