Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer

Uncovering the Importance of Selenium in Muscle Disease

A connection between selenium bioavailability and development of muscular disorders both in humans and livestock has been established for a long time. With the development of genomics, the function of several selenoproteins was shown to be involved in muscle activity, including SELENON, which was linked to an inherited form of myopathy. Development of animal models has helped to dissect the physiological dysfunction due to mutation in the SELENON gene; however the molecular activity remains elusive and only recent analysis using both in vivo and in vitro experiment provided hints toward its function in oxidative stress defence and calcium transport control. This review sets out to summarise most recent findings for the importance of selenium in muscle function and the contribution of this information to the design of strategies to cure the diseases

Immunohistochemical detection of fungal elements in the tissues of goslings with pulmonary and systemic aspergillosis

Nineteen goslings with pulmonary and systemic aspergillosis were the subject of the study. The lungs and air sacs were the main sites affected by the disease, and were generally characterised by diffuse yellowish-white granulomas. In 7 cases with pulmonary and air-sac involvement the granulomas were scattered to the serosal linings of the gastrointestinal and upper respiratory tracts, to the liver, spleen and kidneys, and in two cases also to the bursa of Fabricius, musculus (m.) longus colli and adventitia of aorta. The granulomas were often characterised by a necrotic centre surrounded by heterophils, macrophages, lymphocyte and plasma cells, and in late granulomas by multinucleated foreign-body giant cells, and again by an outer thin fibrous capsule. Numerous fungal hyphae were found within the necrotic debris of the granulomas by Gridley and PAS staining techniques. Immunohistochemistry reliably confirmed aspergillosis in all of the cases. Fungal elements in the lungs of goslings severely affected by the disease stained heavily within the centre of the granulomas, whereas few antigens reacted in the chronic cases. Fungal fragments, which were not discernible using routine fungal stains, reacted clearly in the cytoplasm of macrophages and giant cells. Thus, although fungal elements within the granulomas were histologically indicative of aspergillosis, immunohistochemistry also had to be applied to obtain a definitive diagnosis of the disease and to differentiate it from many of the filamentous fungi