A case series highlighting the role of different gamma-herpesviruses in Equine Multinodular Pulmonary Fibrosis.

INTRODUCTION: This case series describes three cases of equine multinodular pulmonary fibrosis (EMPF) diagnosed at the Clinic for Equine Internal Medicine at the University of Zurich between 2012 and 2017. Current information on etiology and treatment options are presented. Two horses showed mild signs of chronic lower respiratory tract disease and one horse was presented with acute signs of disease including recurrent fever spikes and tachypnea. Diagnosis was achieved by physical examination, radiographic findings, and PCR testing for equine herpesviruses (EHV) of bronchoalveolar lavage (BAL) fluid or lung tissue obtained by biopsy. All horses were euthanized due to continuing deterioration after attempted treatment. Post mortem histological examination of lung tissue showed severe multifocal diffuse to confluent fibrosis in two cases and in another horse a discrete nodular fibrosis pattern. Panherpes nested PCR revealed the presence of equine herpesvirus 5 (EHV-5) DNA in lung tissue of one horse whereas in two other horses, asinine herpes virus 5 (AHV-5) was detected. EMPF should be considered as a differential diagnosis in horses with acute and chronic respiratory disease, including horses non-responsive to treatment for equine asthma.

INTRODUCTION: Cette série de cas décrit trois cas de fibrose pulmonaire multinodulaire équine (EMPF) diagnostiqués à la Clinique de médecine interne équine de l'Université de Zurich entre 2012 et 2017. Des informations actuelles sur l'étiologie et les options de traitement sont présentées. Deux chevaux présentaient de légers signes de maladie chronique des voies respiratoires inférieures et un cheval présentait des signes aigus de maladie, notamment des pics de fièvre récurrents et une tachypnée. Le diagnostic a été obtenu grâce à un examen physique, des résultats radiographiques et des tests PCR pour les virus herpès équins (EHV) du liquide de lavage broncho-alvéolaire (BAL) ou du tissu pulmonaire obtenus par biopsie. Tous les chevaux ont été euthanasiés en raison d'une détérioration continue après une tentative de traitement. L'examen histologique post mortem du tissu pulmonaire a montré une fibrose multifocale diffuse à confluente sévère dans deux cas et chez un cheval un type de fibrose nodulaire discret. La PCR par Panherpes a révélé la présence d'ADN de virus herpès équin 5 (EHV-5) dans le tissu pulmonaire d>un cheval alors que chez deux autres chevaux, le virus de l>herpès asinien 5 (AHV-5) a été détecté. L'EMPF doit être considéré comme un diagnostic différentiel chez les chevaux souffrant d'une maladie respiratoire aiguë et chronique, y compris les chevaux ne répondant pas au traitement de l'asthme équin.

Consistent detection of bovine papillomavirus in lesions, intact skin and peripheral blood mononuclear cells of horses affected by hoof canker.

REASONS FOR PERFORMING THE STUDY: Equine hoof canker is a chronic proliferative pododermatitis of as yet unknown aetiology. Like equine sarcoid disease, canker is a therapy-resistant disorder characterised by hyperkeratosis, acanthosis and a marked tendency to recur. HYPOTHESIS: There is an association of sarcoid-inducing bovine papillomaviruses of types 1 and 2 (BPV-1, BPV-2) with hoof canker disease. METHODS: Using PCR-based techniques, we assessed canker tissue, intact skin and/or peripheral blood mononuclear cells (PBMCs) of 25 canker-affected horses for the presence of sarcoid-associated BPV-1 and -2. RESULTS: Conventional PCR revealed BPV-1/-2 DNA in 24/24 canker, 12/13 skin and 10/11 PBMC DNA isolates. Using inverse PCR, full-length BPV episomes were detected in 1/5 canker specimens. Sequencing of viral early and late genes amplified from canker, intact skin and PBMC DNA of 2 cases revealed an overall identity of 98% to BPV-1. Viral DNA loads amounted to ≤16 copies per cell in canker tissue and intact skin, and to ≤0.35 copies per PBMC, as determined by quantitative PCR. Using RT-PCR, the viral major oncogene E5 was shown to be transcribed in 2/4 canker tissue specimens and 5/7 PBMC isolates. Immunocapture PCR from 7 canker and 6 skin extract supernatants revealed capsomere-associated viral DNA in one canker and one skin sample. Hoof tissue, skin and PBMCs collected from 13 individuals with no signs of canker or BPV-related malignancies scored negative throughout the experiments. CONCLUSION: These findings suggest that the observed presence of BPV-1/-2 in canker-affected horses is not coincidental but indicative of an active contribution to hoof canker disease. POTENTIAL RELEVANCE: The use of antivirals and/or immune modulators may help improving canker therapy.