title: Inoculation of young horses with bovine papillomavirus type 1 virions leads to early infection of PBMCs prior to pseudo-sarcoid formation.
abstract: Bovine papillomavirus types 1 and 2 (BPV-1 and BPV-2) are known to induce common equine skin tumours, termed sarcoids. Recently, it was demonstrated that vaccination with BPV-1 virus-like particles (VLPs) is safe and highly immunogenic in horses. To establish a BPV-1 challenge model for evaluation of the protective potential of BPV-1 VLPs, four foals were injected intradermally with infectious BPV-1 virions and with viral genome-based and control inocula, and monitored daily for tumour development. Blood was taken before inoculation and at weekly intervals. BPV-1-specific serum antibodies were detected by a pseudo-virion neutralization assay. Total nucleic acids extracted from tumours, intact skin and PBMCs were tested for the presence of BPV-1 DNA and mRNA using PCR and RT-PCR, respectively. Intralesional E5 oncoprotein expression was determined by immunofluorescence. Pseudo-sarcoids developed exclusively at sites inoculated with virions. Tumours became palpable 11-32 days after virion challenge, reached a size of ≤20 mm in diameter and then resolved in ≤6 months. No neutralizing anti-BPV-1 serum antibodies were detectable pre- or post-challenge. BPV-1 DNA was present in lesions but not in intact skin. In PBMCs, viral DNA was already detectable before lesions were first palpable, in concentrations correlating directly with tumour growth kinetics. PBMCs from two of two foals also harboured E5 mRNA. Immunofluorescence revealed the presence of the E5 protein in tumour fibroblasts, but not in the apparently normal epidermis overlying the lesions. Together with previous findings obtained in horses and cows, these data suggest that papillomavirus infection may include a viraemic phase.
authors.affiliation: Division of Large Animal Surgery and Orthopaedics, Equine Clinic, Veterinary University Vienna, Vienna, Austria.|Division of Large Animal Internal Medicine, Equine Clinic, Veterinary University Vienna, Vienna, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Hartl
authors.affiliation: Division of Large Animal Surgery and Orthopaedics, Equine Clinic, Veterinary University Vienna, Vienna, Austria.
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Hainisch
authors.affiliation: Laboratory of Viral Oncology, Division of Immunology, Allergy and Infectious Disease, Department of Dermatology, Medical University Vienna, Vienna, Austria.
authors.forename: Saeed
authors.initials: S
authors.lastname: Shafti-Keramat
authors.affiliation: Laboratory of Viral Oncology, Division of Immunology, Allergy and Infectious Disease, Department of Dermatology, Medical University Vienna, Vienna, Austria.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kirnbauer
authors.affiliation: Department of Pathology and Animal Health, Faculty of Veterinary Medicine, University of Naples Federico II, Naples, Italy.
authors.forename: Annunziata
authors.initials: A
authors.lastname: Corteggio
authors.affiliation: Department of Pathology and Animal Health, Faculty of Veterinary Medicine, University of Naples Federico II, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Borzacchiello
authors.affiliation: Department of Hygiene, Microbiology and Social Medicine, Division of Virology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Tober
authors.affiliation: Division of Large Animal Surgery and Orthopaedics, Equine Clinic, Veterinary University Vienna, Vienna, Austria.|Division of Large Animal Internal Medicine, Equine Clinic, Veterinary University Vienna, Vienna, Austria.
authors.forename: Christina
authors.initials: C
authors.lastname: Kainzbauer
authors.affiliation: Division of Large Animal Surgery and Orthopaedics, Equine Clinic, Veterinary University Vienna, Vienna, Austria.|Division of Large Animal Internal Medicine, Equine Clinic, Veterinary University Vienna, Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pratscher
authors.affiliation: Division of Large Animal Surgery and Orthopaedics, Equine Clinic, Veterinary University Vienna, Vienna, Austria.|Division of Large Animal Internal Medicine, Equine Clinic, Veterinary University Vienna, Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Brandt
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D052688:Bovine papillomavirus 1 / Q000472:pathogenicity*; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D004195:Disease Models, Animal; D019085:Fluorescent Antibody Technique, Direct; D006736:Horses; D007963:Leukocytes, Mononuclear / Q000821:virology*; D009500:Neutralization Tests; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012507:Sarcoidosis / Q000473:pathology* / Q000821:virology*; D012867:Skin / Q000473:pathology / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger