Evidence for recent genetic variation in monkeypox viruses

Area of Science:

• Virology
• Genomics
• Molecular Biology

Background:

• Monkeypox virus (MPXV) DNA fragment-size profiles generated by PstI digestion correlate with geographic origin.
• Variations in MPXV genomes were observed, including some in subterminal regions and the central conserved region.

Purpose of the Study:

• To further differentiate MPXV genomes by analyzing a specific region within the central conserved part of the genome.
• To investigate a partially deleted open reading frame (ORF) in MPXV, analogous to intact ORFs in variola and vaccinia viruses.
• To understand the evolutionary dynamics and geographic distribution of MPXV through genetic variation analysis.

Main Methods:

• DNA digestion of MPXV isolates using the endonuclease PstI.
• Analysis of fragment-size profiles to identify genomic variations.
• Sequencing and comparative analysis of a specific ORF region within the central conserved part of the MPXV genome.

Main Results:

• Geographic-specific fragment-size profiles were observed in MPXV DNA.
• A partially deleted ORF was identified in MPXV, with variations (deletions and insertions) distinguishing West African and Zairean isolates.
• Three deletions predating geographic separation and more recent changes differentiating lineages were identified; overall sequence similarity exceeded 99%.

Conclusions:

• Genetic variations in MPXV, particularly in a non-functional ORF, reflect geographic origins and recent evolutionary changes.
• Insertions and deletions appear to be common in poxvirus DNA replication but are only preserved in non-essential genes.
• This genetic analysis provides insights into MPXV evolution and transmission dynamics.