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Postpartum disseminated HSV-1 infection with hemophagocytic lymphohistiocytosis and fulminant neonatal herpes infection

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DOI

  • Mette Ratzer Freytag, Orthopaedic Research Unit, Aarhus University Hospital, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark; Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus N, Denmark.
  • ,
  • Sofie Eg Jørgensen
  • Michelle Mølgaard Thomsen
  • Ali Al-Mousawi, Orthopaedic Research Unit, Aarhus University Hospital, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark; Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus N, Denmark.
  • ,
  • Alon Schneider Hait
  • David Olagnier
  • Jakob T Bay, Department of Oncology, Rigshospitalet, Copenhagen University Hospital; DBCG-secretariat, Department 2501, Rigshospitalet, Copenhagen Ø, Denmark.
  • ,
  • Marie Helleberg, Department of Oncology, Rigshospitalet, Copenhagen University Hospital; DBCG-secretariat, Department 2501, Rigshospitalet, Copenhagen Ø, Denmark.
  • ,
  • Trine H Mogensen

The present study describes a 19-year-old woman with systemic herpes simplex virus (HSV)-1 infection postpartum, and a fatal course of neonatal herpesvirus infection. The mother experienced an unusual disease course with hemophagocytic lymphohistiocytosis (HLH) and persistence of HSV-1 DNA for 15 weeks. Functional investigation of cells from the mother demonstrated significantly impaired induction of antiviral interferons and cytokines in response to viruses and various ligands 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 mutation in CASP8 or other variants in non-coding regions of the genome, contributed to the unusually severe disease course in two generations with disseminated HSV-1 infection evolving into HLH in the mother, and a fatal neonatal HSV-1 infection.

Original languageEnglish
JournalThe Journal of Infectious Diseases
ISSN0022-1899
DOIs
Publication statusE-pub ahead of print - 26 May 2021

Bibliographical note

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

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