# Insights into Genomic Dynamics and Plasticity in the Monkeypox Virus from the 2022 Outbreak

## TL;DR

Researchers analyzed the Monkeypox virus genome during the 2022 outbreak to understand how it adapts, finding specific genetic changes that might help it evade the immune system.

## Contribution

The study introduces STR profiling as a new method to enhance genomic surveillance of Monkeypox virus.

## Key findings

- 19 STR loci were identified near genes involved in immune modulation and virion formation.
- A deletion in STR-VII within OPG153 was found to alter a viral protein's acidic loop without changing its overall structure.
- STR profiling could improve outbreak tracking and understanding of viral adaptation.

## Abstract

The 2022 global mpox outbreak represented a turning point in the Monkeypox virus (MPXV) epidemiology, highlighting the incredible capability of this virus to adapt to different conditions, also in a non-endemic context. To investigate the genomic dynamics of MPXV 2022 strains, we performed whole-genome sequencing of 40 clinical samples from 16 Italian patients across multiple anatomical sites and timepoints between May and December 2022. Combining single-nucleotide analysis with detailed investigation of short tandem repeats (STRs), we explored inter- and intra-host viral dynamics. We identified 19 STR loci located near or within genes involved in immune modulation and virion morphogenesis. While most STRs remained stable across patients, a subset displayed locus- or matrix-specific variation. Among these, STR-VII—embedded within the coding sequence of OPG153, an envelope-associated protein implicated in viral attachment—showed a 12-nucleotide in-frame deletion, resulting in the loss of four aspartic acid residues (Δ4D variant). Structural modeling indicated that this deletion slightly alters a disordered acidic loop without affecting the global fold, potentially modulating surface charge and immune recognition. Integrating STR profiling into genomic surveillance may enhance resolution in outbreak reconstruction and reveal subtle adaptive processes underlying poxvirus–host interaction and immune escape.