Variola Virus and Clade I Mpox Virus Differentially Modulate Cellular Responses Longitudinally in Monocytes During...

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Variola virus (VARV), the cause of smallpox, was eradicated but remains a significant historical pathogen.
• Mpox virus (MPXV) poses a growing global health threat, with increasing cases in endemic and non-endemic regions.
• Understanding conserved molecular pathogenesis between VARV and MPXV is crucial due to clinical similarities.

Purpose of the Study:

• To compare the host cellular responses to VARV and MPXV infections in human monocytes.
• To identify conserved and distinct molecular pathogenesis pathways between these two orthopoxviruses.
• To inform the development of broad-spectrum therapeutics against orthopoxviruses.

Main Methods:

• Longitudinal kinome analysis of human monocytes infected with VARV.
• Comparative analysis of host responses to clade I MPXV infection in human monocytes.
• Validation of identified differences in cell signaling events.

Main Results:

• Both VARV and MPXV induced strong activation of cellular responses early in infection.
• Significant differences in host cell signaling pathways were identified between VARV and MPXV infections.
• Specific key differences in kinome activation were validated.

Conclusions:

• Distinct host-pathogen interactions exist between VARV and MPXV at the molecular level.
• The identified differences in cell signaling provide targets for therapeutic intervention.
• These findings support the development of pan-orthopoxvirus therapeutics for diseases like smallpox and mpox.