Orf virus (ORFV) infection in a three-dimensional human skin model : Characteristic cellular alterations and interference with keratinocyte differentiation

ORF virus (ORFV) is the causative agent of contagious ecthyma, a pustular dermatitis of small ruminants and humans. Even though the development of lesions caused by ORFV was extensively studied in animals, only limited knowledge exists about the lesion development in human skin. The aim of the present study was to evaluate a three-dimensional (3D) organotypic culture (OTC) as a human skin model for ORFV infection considering lesion development, replication of the virus, viral gene transcription and modulation of differentiation of human keratinocytes by ORFV. ORFV infection of OTC was performed using the ORFV isolate B029 derived from a human patient. The OTC sections showed a similar structure of stratified epidermal keratinocytes as human foreskin and a similar expression profile of the differentiation markers keratin 1 (K1), K10, and loricrin. Upon ORFV infection, OTCs exhibited histological cytopathic changes including hyperkeratosis and ballooning degeneration of the keratinocytes. ORFV persisted for 10 days and was located in keratinocytes of the outer epidermal layers. ORFV-specific early, intermediate and late genes were transcribed, but limited viral spread and restricted cell infection were noticed. ORFV infection resulted in downregulation of K1, K10, and loricrin at the transcriptional level without affecting proliferation as shown by PCNA or Ki-67 expression. In conclusion, OTC provides a suitable model to study the interaction of virus with human keratinocytes in a similar structural setting as human skin and reveals that ORFV infection downregulates several differentiation markers in the epidermis of the human skin, a hitherto unknown feature of dermal ORFV infection in man.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:14

Enthalten in:

PloS one - 14(2019), 1 vom: 30., Seite e0210504

Sprache:

Englisch

Beteiligte Personen:

Muhsen, Mahmod [VerfasserIn]
Protschka, Martina [VerfasserIn]
Schneider, Laura E [VerfasserIn]
Müller, Uwe [VerfasserIn]
Köhler, Gabriele [VerfasserIn]
Magin, Thomas M [VerfasserIn]
Büttner, Mathias [VerfasserIn]
Alber, Gottfried [VerfasserIn]
Siegemund, Sabine [VerfasserIn]

Links:

Volltext

Themen:

68238-35-7
Journal Article
Keratins
Loricrin
Membrane Proteins
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 18.11.2019

Date Revised 05.10.2023

published: Electronic-eCollection

Citation Status MEDLINE

doi:

10.1371/journal.pone.0210504

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM293261024