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Peer reviewedOpen accessMonkeypox

Monkeypox virus clade IIb isolate exhibits reduced virulence relative to clade IIa isolates in multiple murine models

Journal of Virology·

Stephanie V. Trefry, Santiago Vidal-Freire, Mayanka Awasthi, Abel D. Ordonez, Brett P. Eaton, Randy J. Hart, Christy N. Raney, Amy L. Cregger, Chase A. Gonzales, Robert N. Enamorado, Nelson A. Martinez, Deborah S. Gohegan, Matthew G. Lackemeyer, Tinoush Moulaei, Natasza E. Ziółkowska, Jeremy J. Bearss, Scott J. Goebel, Gustavo Palacios, Sina Bavari, Farooq Nasar

DOI
10.1128/jvi.00247-26
PMID
42454914
PMCID
OpenAlex
W4417261573
Study type
Journal article
Publisher
American Society for Microbiology
Article type
journal-article
Integrity
current

Why this research matters now

Validating these murine platforms facilitates ongoing research into viral mechanisms and supports the evaluation of potential therapeutic strategies against divergent orthopoxvirus lineages.

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Structured evidence summary

Research question

This study evaluates how two distinct monkeypox virus subclades differ in pathogenicity across various laboratory mouse strains and determines which genetic backgrounds effectively support viral replication.

Study design

A controlled laboratory experiment comparing disease outcomes in four murine strains following standardized viral inoculation with specific clade IIa and IIb isolates.

Population and setting

Four murine cohorts consisting of a standard wild-type line and three immunodeficient variants engineered to lack specific interferon receptor pathways.

Main findings

Clade IIa isolates consistently produced severe clinical deterioration and high mortality across all tested mouse strains. In contrast, clade IIb isolates generated only mild symptoms at equivalent dosages, with fatal outcomes restricted to the highest concentration administered to the most immunocompromised group. Quantitative comparisons indicate that clade IIa demonstrates substantially greater pathogenicity than clade IIb.

Public-health relevance

Validating these murine platforms facilitates ongoing research into viral mechanisms and supports the evaluation of potential therapeutic strategies against divergent orthopoxvirus lineages.

Important limitations

The authors acknowledge that previous investigations were constrained by an insufficient availability of appropriate small animal models for studying these viral variants.

GIDS interpretation

This manuscript adds methodological resources and comparative virology data to the academic record, improving the capacity to characterize emerging viral subclades through established laboratory frameworks.

02

Related GIDS surveillance

Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.

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Evidence relationships

This article has 7 auditable classifier relationships to diseases, places, topics, and study design.

about diseaseaddresses topicaddresses topichas pathogen typestudied population settingstudies pathogenuses study design