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The antimicrobial protein RNase 7 directly restricts herpes simplex virus infection of human keratinocytes
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  • Jana Zeitvogel,
  • Katinka Döhner,
  • Ilona Klug,
  • Franziska Rademacher,
  • Regine Gläser,
  • Beate Sodeik,
  • Jürgen Harder,
  • Thomas Werfel
Jana Zeitvogel
Hannover Medical School
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Katinka Döhner
Hannover Medical School

Corresponding Author:[email protected]

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Ilona Klug
Hannover Medical School
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Franziska Rademacher
Kiel University
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Regine Gläser
Kiel University
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Beate Sodeik
Cluster of Excellence RESIST (EXC 2155) Hannover Medical School
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Jürgen Harder
Kiel University
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Thomas Werfel
Hannover Medical School
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Abstract

Approximately 22% of moderately to severely affected atopic dermatitis (AD) patients have a history of eczema herpeticum, a disseminated rash primarily caused by herpes simplex virus type 1 (HSV-1). Reduced activity of antimicrobial peptides may contribute to the increased susceptibility of AD patients to HSV-1. We previously demonstrated that the antimicrobial protein RNase 7 promotes self-DNA sensing by human keratinocytes, thereby strengthening their resistance to HSV-1 infection. Here, we investigated the effects of RNase 7 in the absence of exogenously added costimulatory DNA. Recombinant RNase 7 restricted HSV-1 gene expression, genome replication, and plaque formation in human keratinocytes. It decreased HSV-1 immediate-early transcripts independently of the induction of interferon-stimulated genes. Its main effect was on intracellular infection processes and not on extracellular virions or virus binding to cells. RNase 7 reduced the amount of cell-associated capsids and the HSV-1 envelope glycoprotein D at 3 but not at 0.5 h post-infection, suggesting that it promoted the degradation of incoming viral particles. Our data show that RNase 7 directly restricts HSV-1 infection of human keratinocytes, suggesting that it limits HSV-1 spread in the skin, and thereby disseminated infection. Previously described mechanisms that reduce RNase 7 activity in the lesional skin of AD patients may increase their susceptibility to eczema herpeticum.
Submitted to Journal of Medical Virology
Submission Checks Completed
Assigned to Editor
Reviewer(s) Assigned
20 Jun 2024Review(s) Completed, Editorial Evaluation Pending
20 Jun 2024Reviewer(s) Assigned
29 Aug 20241st Revision Received
03 Sep 2024Submission Checks Completed
03 Sep 2024Assigned to Editor
03 Sep 2024Review(s) Completed, Editorial Evaluation Pending
03 Sep 2024Reviewer(s) Assigned
16 Sep 2024Editorial Decision: Accept