Unveiling Intra-Clonal Diversity of Monkeypox Virus from Brazil's First Outbreak Wave

Area of Science:

• Virology
• Genomics
• Infectious Diseases

Background:

• Monkeypox virus (MPXV) causes mpox, an emerging zoonotic disease with smallpox-like symptoms.
• The 2022 global mpox outbreak involved over 162,000 cases across 140 countries.
• Understanding MPXV intra-clonal diversity is crucial for tracking viral evolution and spread.

Purpose of the Study:

• To analyze the intra-clonal diversity of MPXV from a single patient lesion.
• To compare MPXV clone characteristics with vaccinia virus Western Reserve (VACV-WR).
• To identify genetic variations within MPXV clones and their relation to reference strains.

Main Methods:

• Isolation and characterization of three MPXV viral clones from a patient skin lesion.
• Phenotypic evaluation of MPXV lysis plaque characteristics in BSC-40 cells.
• Whole-genome sequencing, comparative genomics, synteny analysis, and single nucleotide variation (SNV) calling.

Main Results:

• MPXV clones did not exhibit comet-like structures, unlike VACV-WR, indicating potentially reduced extracellular enveloped virus (EEV) release.
• Whole-genome sequencing revealed subtle genetic differences among MPXV clones.
• Comparative genomic analyses showed intra-clonal divergence from clade I and II references, but without significant protein-level variations.

Conclusions:

• Distinct MPXV variants can potentially circulate concurrently within a single mpox lesion.
• Subtle genomic differences among MPXV clones suggest ongoing viral evolution.
• Further research is needed to understand the functional implications of intra-clonal MPXV diversity.