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In a collaborative study between researchers at Mount Sinai and the Carlos III Health Institute in Madrid, alterations in the monkeypox virus genome that potentially correlate with changes in the virus’s transmissibility during the 2022 outbreak were located and identified. Monkeypox virus (MPXV) is a double-stranded DNA virus that can infect animals and humans, causing a disease known as mpox with symptoms of fever, swollen lymph nodes, and a rash. Since its first encounter in 1958, outbreaks of MPXV have occurred sporadically in Central and Western Africa. In the 2022 outbreak, an increasing number of MPXV infections and associated disease were reported in multiple countries, including the United States, with clusters of cases potentially linked to super-spreading events in Europe. As the virus continues to circulate in humans, the risk of more transmissible variants emerging and becoming endemic increases.

The researchers emphasized the importance of biopreparedness and virological surveillance in studying the conditions that favor zoonotic spillover and human-to-human transmission. With significant changes in the basic epidemiological features of the virus observed during the 2022 outbreak, there is a need to understand the transmission conditions to prevent further spread of the virus. The current increase in MPXV cases in Africa and the 2022 epidemic serve as clear alert signals for continued monitoring and research efforts. The study focused on analyzing samples from 46 patients infected with MPXV during the 2022 outbreak to determine possible correlations between genomic variations and epidemiological links associated with the virus’s ability to evolve, transmit, and infect.

The research team identified recurrent genomic changes in specific areas of the MPXV genome that could be related to viral adaptation, affecting viral replication, adaptability, and path of entry and egress. These alterations were found in low complexity genomic regions, which are challenging to sequence and analyze but play a crucial role in the virus’s evolution and transmissibility. Utilizing advanced sequencing technologies, including single-molecule long-read sequencing and deep short sequencing reads, enabled the team to perform high-quality sequencing of each participant’s complete monkeypox virus genome, providing insights into the virus’s ability to spread and infect. By detailing the genomic alterations within these repetitive sequences and linking them to critical viral functions, researchers offer a plausible explanation for the heightened transmissibility observed during the 2022 outbreak.

The study’s findings provide valuable insights into the unique features of the strains associated with sustained human-to-human transmission of MPXV, a phenomenon not previously observed with these agents. Understanding the mechanisms that facilitate viral transmission and impact clinical presentations will aid in the development of more effective prevention and treatment strategies. The researchers believe that these discoveries offer a starting point for further research to enhance our understanding of viral evolution and transmission dynamics, ultimately improving our ability to respond to future outbreaks and prevent the emergence of more transmissible variants. Continued surveillance and research efforts are essential to stay ahead of emerging infectious diseases like monkeypox and protect public health.

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