Mount Sinai scientists, in collaboration with researchers from the Instituto de Salud Carlos III (ISCIII) in Madrid, Spain, have located and identified alterations in the monkeypox virus genome that potentially correlate with changes in the transmissibility of the virus. observed in the 2022 outbreak. The findings were published on April 18 in Nature communications.
Monkeypox virus (MPXV) is a double-stranded DNA virus that can infect animals and humans. MPXV causes a disease known as mpox, with symptoms including fever, swollen lymph nodes, and rash. Most cases are mild and tend to get better on their own; However, mpox can be very painful and cause permanent scarring. MPXV, which was first found in 1958 in cynomolgus macaque monkeys imported to Belgium, has caused sporadic outbreaks of human disease since the 1970s in central and western Africa. In May 2022, several countries, including the United States, reported increasing numbers of MPXV infections and associated illnesses, including clusters of cases potentially linked to super-spreading events in Belgium, Spain, and the United Kingdom. While the number of new cases associated with the 2022 contagion has decreased over time, cases of the disease still occur among unvaccinated people, including a current increase in Central Africa due to a new contagion. As circulation of the virus in humans increases, the risk of the emergence of a more transmissible variant capable of becoming endemic in the human population increases.
“Biopreparing and virological surveillance involve studying the causes that promote zoonotic spillover and facilitate human-to-human transmission. When we see significant changes in the basic epidemiological characteristics of a viral agent such as monkeypox, it should reinvigorate our interest in understanding those transmission conditions. The increasing number of cases currently occurring in Africa and the 2022 epidemic should be clear warning signs,” says Gustavo Palacios, PhD, professor of Microbiology at the Icahn School of Medicine at Mount Sinai and senior author of the study. .
To conduct the study, the researchers analyzed samples from 46 MPXV-infected patients whose diagnosis and sequencing were performed at ISCIII at the beginning of the 2022 MPXV outbreak. The team performed high-quality sequencing of the entire genome of the smallpox virus. monkey from each study participant to determine possible correlations between genomic variations in different sequence groups and epidemiological links associated with the virus’s ability to evolve, transmit, and infect.
According to the research team, the recurrently observed genomic changes were located in areas of the genome that could be related to viral adaptation. These specific locations would contribute to modulating the viral replication cycle, adaptability, and the entry and exit route. These alterations appear in areas known as low-complexity genomic regions, which are particularly difficult to sequence and analyze, which explains why they were previously overlooked. This highly sophisticated whole genome sequencing was made possible through the use of two advanced sequencing technologies: single-molecule long-read sequencing (to cover highly repetitive regions) and short, deep-read sequencing (to provide accuracy and depth).
By detailing the genomic alterations within these repetitive genomic sequences and linking them to critical viral functions, the researchers provide a plausible explanation for the increased transmissibility observed during the 2022 mpox outbreak.
“These findings could offer the first clues to help us understand the unique characteristics of strains associated with sustained human-to-human transmission, which have never been observed in these agents,” says Dr. Palacios. “A better understanding of the gates that facilitate the transmission of viral agents and affect their clinical presentations will allow us to develop more effective prevention and treatment strategies.”