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<p>The recently emerged clade Ib of mpox virus (MPXV) is spreading rapidly across Central and West Africa raising concerns about its potential virulence. Similar to clade IIb lineage B.1, which was responsible for the 2022 global outbreak, clade Ib exhibits sustained human-to-human transmission and a pattern of APOBEC3-associated genomic mutations. Here, we show that clade Ib displays enhanced long-range spreading in cell culture compared to clade IIb. Additionally, using the CAST mouse model, we show that clade Ib exhibits a higher level of virulence compared to the markedly attenuated clade IIb. Clade Ib leads to significant weight loss and high mortality in animals following both intraperitoneal and intranasal challenge. Histopathological analysis revealed more severe and extensive lung lesions in clade Ib–infected animals, accompanied by a broader distribution of viral antigens. Moreover, clade Ib, unlike IIb, disseminated efficiently to internal organs. These findings indicate that clade Ib MPXV has not undergone attenuation after human-to-human transmission to the extent observed in clade IIb and underscore the need for surveillance and preparedness against new emerging MPXV lineages.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月11日

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  • Alazne R. Unanue,
  • Rocío Martín,
  • Carolina Sánchez,
  • Isabel Alonso-Sánchez,
  • Ana Moraga-Quintanilla,
  • Laura Fernandez del Ama,
  • Pedro J. Sánchez-Cordón,
  • Antonio Alcamí,
  • Bruno Hernáez

摘要

The recently emerged clade Ib of mpox virus (MPXV) is spreading rapidly across Central and West Africa raising concerns about its potential virulence. Similar to clade IIb lineage B.1, which was responsible for the 2022 global outbreak, clade Ib exhibits sustained human-to-human transmission and a pattern of APOBEC3-associated genomic mutations. Here, we show that clade Ib displays enhanced long-range spreading in cell culture compared to clade IIb. Additionally, using the CAST mouse model, we show that clade Ib exhibits a higher level of virulence compared to the markedly attenuated clade IIb. Clade Ib leads to significant weight loss and high mortality in animals following both intraperitoneal and intranasal challenge. Histopathological analysis revealed more severe and extensive lung lesions in clade Ib–infected animals, accompanied by a broader distribution of viral antigens. Moreover, clade Ib, unlike IIb, disseminated efficiently to internal organs. These findings indicate that clade Ib MPXV has not undergone attenuation after human-to-human transmission to the extent observed in clade IIb and underscore the need for surveillance and preparedness against new emerging MPXV lineages.