phaidra.vetmeduni.ac.at o:1241 DOI 10.3390/v14122658 Bovine Papillomavirus Type 1 or 2 Virion-Infected Primary Fibroblasts Constitute a Near-Natural Equine Sarcoid Model Equine sarcoids are common, locally aggressive skin tumors induced by bovine papillomavirus types 1, 2, and possibly 13 (BPV1, BPV2, BPV13). Current in vitro models do not mimic de novo infection. We established primary fibroblasts from horse skin and succeeded in infecting these cells with native BPV1 and BPV2 virions. Subsequent cell characterization was carried out by cell culture, immunological, and molecular biological techniques. Infection of fibroblasts with serial 10-fold virion dilutions (2 × 106-20 virions) uniformly led to DNA loads settling at around 150 copies/cell after four passages. Infected cells displayed typical features of equine sarcoid cells, including hyperproliferation, and loss of contact inhibition. Neither multiple passaging nor storage negatively affected cell hyperproliferation, viral DNA replication, and gene transcription, suggestive for infection-mediated cell immortalization. Intriguingly, extracellular vesicles released by BPV1-infected fibroblasts contained viral DNA that was most abundant in the fractions enriched for apoptotic bodies and exosomes. This viral DNA is likely taken up by non-infected fibroblasts. We conclude that equine primary fibroblasts stably infected with BPV1 and BPV2 virions constitute a valuable near-natural model for the study of yet unexplored mechanisms underlying the pathobiology of BPV1/2-induced sarcoids. eng Horse Sarcoid Bovine Papillomavirus BPV1 BPV2 Virions Primary Fibroblasts In Vitro Model 2023-02-09T13:09:37.488Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Hainisch;Edmund K; FN:Edmund K Hainisch END:VCARD BEGIN:VCARD VERSION:3.0 N:Jindra;Christoph; FN:Christoph Jindra END:VCARD BEGIN:VCARD VERSION:3.0 N:Reicher;Paul; FN:Paul Reicher END:VCARD BEGIN:VCARD VERSION:3.0 N:Miglinci;Lea; FN:Lea Miglinci X-ORCID:https://orcid.org/0000-0002-6050-8848 END:VCARD BEGIN:VCARD VERSION:3.0 N:Brodesser;Daniela M; FN:Daniela M Brodesser X-ORCID:https://orcid.org/0000-0002-0558-7889 END:VCARD BEGIN:VCARD VERSION:3.0 N:Brandt;Sabine; FN:Sabine Brandt X-ORCID:https://orcid.org/0000-0002-3837-3422 END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by/4.0 application/pdf 1969757 https://phaidra.vetmeduni.ac.at/o:1241 https://phaidra.vetmeduni.ac.at/api/object/o:1241/thumbnail LOMv1.0 discipline