Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
J Infect Dis. 2022 Jan 5;225(1):157-162. doi: 10.1093/infdis/jiab290.
The present study describes a 19-year-old woman with systemic herpes simplex virus (HSV)-1 infection and hemophagocytic lymphohistiocytosis (HLH) postpartum, and a fatal course of neonatal herpesvirus infection. Functional investigation of cells from the mother demonstrated significantly impaired induction of antiviral interferons and cytokines in the context of normal activation of the transcription factors NF-κB and IRF3. Whole-exome sequencing did not reveal any functionally validated genetic variants. We suggest that the functionally impaired antiviral responses, potentially caused by a variant in CASP8 or other variants in noncoding regions of the genome, contributed to the unusually severe disease course observed in two generations.
本研究描述了一例 19 岁女性患者在产后发生全身性单纯疱疹病毒（HSV-1）感染和噬血细胞性淋巴组织细胞增生症（HLH），并导致新生儿疱疹病毒感染的致命病程。对母亲细胞的功能研究表明，在 NF-κB 和 IRF3 转录因子正常激活的情况下，抗病毒干扰素和细胞因子的诱导显著受损。全外显子组测序未发现任何具有功能验证的遗传变异。我们推测，抗病毒反应功能受损，可能是由于 CASP8 或基因组非编码区域的其他变异引起的，导致了两代人中观察到的异常严重疾病过程。
