Postpartum Disseminated Herpes Simplex Virus Type 1 Infection With Hemophagocytic Lymphohistiocytosis and Fulminant Neonatal Herpes Infection

J Infect Dis. 2022 Jan 5;225(1):157-162. doi: 10.1093/infdis/jiab290.

Abstract

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.

Keywords: hemophagocytic lymphohistiocytosis; herpes simplex virus; innate immunity; interferon; neonatal herpes.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use
  • Communicable Diseases / drug therapy
  • Cytokines
  • Exome Sequencing
  • Female
  • Herpes Simplex / complications
  • Herpes Simplex / diagnosis*
  • Herpes Simplex / drug therapy
  • Herpes Simplex / mortality
  • Herpesvirus 1, Human / genetics
  • Herpesvirus 1, Human / isolation & purification*
  • Humans
  • Immunity, Innate
  • Infectious Disease Transmission, Vertical
  • Interferons / therapeutic use
  • Lymphohistiocytosis, Hemophagocytic / complications*
  • Lymphohistiocytosis, Hemophagocytic / drug therapy
  • Postpartum Period
  • Pregnancy Complications, Infectious
  • Young Adult

Substances

  • Antiviral Agents
  • Cytokines
  • Interferons

Supplementary concepts

  • Neonatal herpes