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

Title: Insights into Genomic Dynamics and Plasticity in the Monkeypox Virus from the 2022 Outbreak
Authors: Michela Deiana; Elena Locatelli; Laura Veschetti; Simone Malagò; Antonio Mori; Denise Lavezzari; Silvia Accordini; Niccolò Ronzoni; Andrea Angheben; Giovanni Malerba; Evelina Tacconelli; Maria Grazia Cusi; Federico Giovanni Gobbi; Chiara Piubelli; Concetta Castilletti
Source: International Journal of Molecular Sciences ; Volume 27 ; Issue 3 ; Pages: 1371
Publisher Information: Multidisciplinary Digital Publishing Institute
Publication Year: 2026
Collection: MDPI Open Access Publishing
Subject Terms: Mpox; Monkeypox virus (MPXV); 2022 outbreak; short tandem repeats (STRs); viral evolution; whole genome sequencing; Orthopoxvirus; structural modeling
Description: 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.
Document Type: text
File Description: application/pdf
Language: English
Relation: Molecular Pathology, Diagnostics, and Therapeutics; https://dx.doi.org/10.3390/ijms27031371
DOI: 10.3390/ijms27031371
Availability: https://doi.org/10.3390/ijms27031371
Rights: https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.92AEC9F4
Database: BASE