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Enhanced virulence of mpox virus clade Ib over clade IIb in the CAST/EiJ mouse model

Alazne R Unanue1, Rocío Martín1, Carolina Sánchez1

  • 1Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain.

Communications Biology
|February 11, 2026
PubMed

Insights

The new mpox virus (MPXV) clade Ib spreads faster and is more virulent than clade IIb, causing severe illness and death in mice. Continued surveillance of emerging MPXV clades is crucial.

Area of Science:

  • Virology
  • Infectious Diseases
  • Public Health

Background:

  • Mpox virus (MPXV) clade Ib is emerging in Africa, showing sustained human-to-human transmission.
  • Clade Ib shares genomic features with clade IIb, the lineage responsible for the 2022 global outbreak.
  • Concerns exist regarding the potential virulence of emerging MPXV clades.

Purpose of the Study:

  • To compare the in vitro spreading capacity of MPXV clade Ib and clade IIb.
  • To evaluate the in vivo virulence of MPXV clade Ib in a mouse model.
  • To assess the pathological effects and organ dissemination of MPXV clade Ib infection.

Main Methods:

  • Cell culture experiments to assess viral spreading.
  • CAST mouse model for intraperitoneal and intranasal MPXV challenge.
  • Histopathological analysis and viral antigen distribution assessment.

Main Results:

  • MPXV clade Ib demonstrated enhanced long-range spreading in cell culture compared to clade IIb.
  • Clade Ib exhibited significantly higher virulence in mice, causing weight loss and mortality.
  • Severe lung lesions and efficient dissemination to internal organs were observed in clade Ib-infected mice.

Conclusions:

  • MPXV clade Ib possesses increased virulence and spreading capacity compared to the attenuated clade IIb.
  • Clade Ib has not undergone significant attenuation following human-to-human transmission.
  • Enhanced surveillance and preparedness are necessary for emerging MPXV clades.

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