Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA.
Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
J Infect Dis. 2024 Mar 26;229(Supplement_2):S265-S274. doi: 10.1093/infdis/jiad516.
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.
天花病毒（VARV）是天花的病原体，在被根除之前对全球健康产生了巨大影响。在没有全球疫苗接种计划的情况下，猴痘病毒（MPXV）已成为一个日益严重的公共卫生威胁，包括全球流行和非流行地区。虽然人类猴痘在临床表现上与天花相似，但这两种正痘病毒之间在保守的分子发病机制方面仍存在相当大的知识空白。因此，我们试图通过激酶组分析比较 MPXV 和 VARV 感染人类单核细胞的情况。我们对人类单核细胞中 VARV 感染的宿主细胞反应进行了纵向分析，并与 I 型猴痘病毒介导的反应进行了比较分析。虽然与后期时间点相比，两种病毒在感染早期都强烈激活了细胞反应，但我们发现并验证了几个关键的细胞信号事件存在差异。这些观察结果将有助于设计和开发泛正痘病毒治疗药物。
