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

Variola virus (VARV), the etiological agent of smallpox, had enormous impacts on global health prior to its eradication. In the absence of global vaccination programs, mpox virus (MPXV) has become a growing public health threat that includes endemic and nonendemic regions across the globe. While hum...

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Bibliographic Details
Published in:The Journal of infectious diseases 2024-03, Vol.229 (Supplement_2), p.S265-S274
Main Authors: Wahl, Victoria, Olson, Victoria A, Kondas, Ashley V, Jahrling, Peter B, Damon, Inger K, Kindrachuk, Jason
Format: Article
Language:English
Subjects:
Humans
Monkeypox virus
Monocytes
Orthopoxvirus
Smallpox
Supplement
Variola virus
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Summary:Variola virus (VARV), the etiological agent of smallpox, had enormous impacts on global health prior to its eradication. In the absence of global vaccination programs, mpox virus (MPXV) has become a growing public health threat that includes endemic and nonendemic regions across the globe. While human mpox resembles smallpox in clinical presentation, there are considerable knowledge gaps regarding conserved molecular pathogenesis between these 2 orthopoxviruses. Thus, we sought to compare MPXV and VARV infections in human monocytes through kinome analysis. We performed a longitudinal analysis of host cellular responses to VARV infection in human monocytes as well as a comparative analysis to clade I MPXV-mediated responses. While both viruses elicited strong activation of cell responses early during infection as compared to later time points, several key differences in cell signaling events were identified and validated. These observations will help in the design and development of panorthopoxvirus therapeutics.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiad516