Researchers assess the evolution and diversity of monkeypox virus genomes using phylogenomic analysis

By Bhavana KunkalikarReviewed by Danielle Ellis, B.Sc.Jul 18 2022

In a recent study published in Travel Medicine and Infectious Disease, researchers phylogenomically analyzed the monkeypox virus (MPXV).

Background

Since May 2022, there have been various reports of increasing MPVX infections in non-endemic countries globally. The ongoing coronavirus disease 2019 (COVID-19) pandemic has highlighted the importance of genomic surveillance to monitor the evolution of pathogens that threaten public health.  

About the study

In the present study, researchers assessed the evolution and diversity of MPVX genomes using phylogenomic analysis.

The team analyzed a total of 337 high-quality and whole MPVX genomic data available in the Global Initiative on Sharing All Influenza Data (GISAID) and viral National Center for Biotechnology Information (NCBI) databases from 29 June 2022. The analysis was performed as per the following scheme. The team aligned the genomic data using the NextClade v2.1.0 tool, followed by the descriptive analysis of the aligned genomes as well as the number of MPVX infections. Subsequently, the team analyzed the phylogenomic relationships between the genomics sequences available publicly.

The phylogenomic analysis was performed using the aligned dataset derived using NextClade. The datasets were utilized to develop a maximum likelihood (ML) further. Furthermore, the team evaluated the potential introduction date as well as the dispersion dynamics of the MPVX infections. The tree obtained from this evaluation was represented in the Interactive Tree Of Life (iTOL), wherein the clades were assigned based on the intrataxa classification system. This system was used since it accurately described the viral diversity and included viruses belonging to the animal reservoirs as well as past human outbreaks, including MPXV clades 1, 2, and 3.

Results

The study results showed that non-endemic countries, including Spain, England, and Germany reported the highest number of MPXV cases. Moreover, 32.6% of the genomic sequences available publicly were obtained from Germany, while 13.4% were obtained from Portugal. Furthermore, among the genomes derived from non-endemic areas, 77.4% belonged to the B1 lineage of the MPXV Clade 3, 10.4% to the MPXV Clades 1, and 2.5% to MPXV Clades 2. Between 1970 and 1996, the years of the first and second MPXV outbreaks, MPXV was found in endemic countries, including the Democratic Republic of Congo (DRC), Cameroon, and Nigeria. However, the third outbreak in 2003 detected the presence of the MPXV genomes in non-endemic countries.

The maximum-likelihood time-scaled phylogeny (ML-TSP) revealed that the three main MPXV clades showed clustering of viral sequences derived from animal reservoirs and past infection outbreaks in humans. These three clades were found to be monophyletic and comprised: (1) 35 human MPXV genomes that were related to the outbreaks incident in Central Africa between 1970 and 2017, (2) MPXV Clade 2 having 16 genomes belonging to different countries detected between 1970 and 2017, and (3) MPXV Clade 3 having 286 genomes belonging to the outbreaks that occurred between 2017 and 2022. Clade 3 included the human MPXV-1A clade as well as the novel lineages of A.1, A.1.1, and B1, wherein B.1 included the MPXV genomes detected in the 2022 MPXV outbreak. Furthermore, the time-scaled phylogeny revealed that the most ancestral cluster was MPXV Clade 1, while the most recent clusters were the hMPXV-1A clades. 

Conclusion

The study findings showed that all the genomes detected in the current MPXV outbreak among humans in 2022 have a remarkable monophyletic lineage compared to the lineages observed in the past human MPXV outbreaks. This striking divergence from the past lineages highlights the increased mutational signature, indicating an accelerated evolutionary path. The study suggested that the noted genomic variations could be responsible for the efficient transmission and the increased number of MPXV infections observed in the 2022 MPXV outbreak.