Exogenous Jaagsiekte Sheep Retrovirus type 2 (exJSRV2) related to ovine pulmonary adenocarcinoma (OPA) in Romania: prevalence, anatomical forms, pathological description, immunophenotyping and virus identification

Corina Toma,Marian Taulescu,Alexandra Rema,Roxana Popa,Adrian Trifa,Adrian Trifa,Septiumiu Tripon,Valentin Adrian Bâlteanu,Raluca Maria Pop,Irina Amorim,Cornel Catoi

doi:10.1186/s12917-020-02521-1

Abstract

BackgroundOvine pulmonary adenocarcinoma (OPA) is a neoplastic disease caused by exogenous Jaagsiekte Sheep Retrovirus (exJSRV). The prevalence of JSRV-related OPA in Eastern European countries, including Romania is unknown.We aimed to investigate: the prevalence and morphological features of OPA (classical and atypical forms) in the Transylvania region (Romania), the immunophenotype of the pulmonary tumors and their relationships with exJSRV infection. A total of 2693 adult ewes slaughtered between 2017 and 2019 in two private slaughterhouses from Transylvania region (Romania) was evaluated. Lung tumors were subsequently assessed by cytology, histology, immunocytochemistry, immunohistochemistry, electron microscopy and DNA testing.ResultsOut of 2693 examined sheep, 34 had OPA (1.26% prevalence). The diaphragmatic lobes were the most affected. Grossly, the classical OPA was identified in 88.24% of investigated cases and the atypical OPA in 11.76% that included solitary myxomatous nodules. Histopathology results confirmed the presence of OPA in all suspected cases, which were classified into acinar and papillary types. Myxoid growths (MGs) were diagnosed in 6 classical OPA cases and in 2 cases of atypical form. Lung adenocarcinoma was positive for MCK and TTF-1, and MGs showed immunoreaction for Vimentin, Desmin and SMA; Ki67 expression of classical OPA was higher than atypical OPA and MGs. JSRV-MA was identified by IHC (94.11%) in both epithelial and mesenchymal cells of OPA. Immunocytochemistry and electron microscopy also confirmed the JSRV within the neoplastic cells. ExJSRV was identified by PCR in 97.05% of analyzed samples. Phylogenetic analysis revealed the presence of the exJSRV type 2 (MT809678.1) in Romanian sheep affected by lung cancer and showed a high similarity with the UK strain (AF105220.1).ConclusionsIn this study, we confirmed for the first time in Romania the presence of exJSRV in naturally occurring OPA in sheep. Additionally, we described the first report of atypical OPA in Romania, and to the best of our knowledge, in Eastern Europe. Finally, we showed that MGs have a myofibroblastic origin.

Highlights

Ovine pulmonary adenocarcinoma (OPA) is a neoplastic disease caused by exogenous Jaagsiekte Sheep Retrovirus
Lung adenocarcinoma was positive for MCK and 1-thyroid transcription factor 1 (TTF)-1, and Myxoid growths (MGs) showed immunoreaction for Vimentin, Desmin and Smooth muscle actin (SMA); Ki67 expression of classical OPA was higher than atypical OPA and MGs
Phylogenetic analysis revealed the presence of the exogenous Jaagsiekte Sheep Retrovirus (exJSRV) type 2 (MT809678.1) in Romanian sheep affected by lung cancer and showed a high similarity with the United Kingdom (UK) strain (AF105220.1)

Summary

Introduction

Ovine pulmonary adenocarcinoma (OPA) is a neoplastic disease caused by exogenous Jaagsiekte Sheep Retrovirus (exJSRV). Ovine pulmonary adenocarcinoma (OPA) represents a virus-related neoplastic disease caused by an exogenous betaretrovirus [1]. ExJSRV has a specific tropism for the differentiated epithelial cells (type II pneumocytes and nonciliated bronchiolar Clara cells) of the lung, and it is the only virus known to cause pulmonary adenocarcinoma in naturally infected animals [8]. ExJSRV is mainly transmitted by infected aerosols [9, 10], and in natural cases the incubation period is very long, ranging from 2 to 4 years It is most often encountered in adult sheep [11], but the lambs can manifest clinical signs [6]. Other animal species, including goats and moufflons were occasionally diagnosed with OPA [9, 13]

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