The antimicrobial protein RNase 7 directly restricts herpes simplex virus infection of human keratinocytes.

Publisher: Wiley-Liss Country of Publication: United States NLM ID: 7705876 Publication Model: Print Cited Medium: Internet ISSN: 1096-9071 (Electronic) Linking ISSN: 01466615 NLM ISO Abbreviation: J Med Virol Subsets: MEDLINE

Publication: New York Ny : Wiley-Liss
Original Publication: New York, Liss.

Keratinocytes*/virology ; Herpesvirus 1, Human*/genetics ; Herpesvirus 1, Human*/physiology ; Ribonucleases*/metabolism ; Ribonucleases*/genetics ; Virus Replication*; Humans ; Viral Plaque Assay ; Cells, Cultured

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 limits HSV-1 infection of human keratinocytes by promoting self-DNA sensing. Here, we addressed whether RNase 7 has any effect on HSV-1 infection when infecting keratinocytes without exogenously added costimulatory DNA, and which step(s) of the infection cycle RNase 7 interferes with. We quantified viral gene expression by RT-qPCR and flow cytometry, viral genome replication by qPCR, virucidal effects by plaque titration, and plaque formation and the subcellular localization of incoming HSV-1 particles by microscopy. 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 postinfection. Our data show that RNase 7 directly restricts HSV-1 infection of human keratinocytes, possibly by promoting the degradation of incoming HSV-1 particles. This suggests that RNase 7 may limit HSV-1 spread in the skin and that mechanisms that reduce its activity in the lesional skin of AD patients may increase their susceptibility to eczema herpeticum.
(© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

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Deutsche Forschungsgemeinschaft

Keywords: RNase 7; antimicrobial peptides and proteins; atopic dermatitis; eczema herpeticum; herpes simplex virus; keratinocytes; restriction of viral infection; skin infection

EC 3.1.27.- (Ribonuclease 7)
EC 3.1.- (Ribonucleases)

Date Created: 20241003 Date Completed: 20241003 Latest Revision: 20241003

20241004

10.1002/jmv.29942

39360648