Association between genetic clades and cancer prevalence suggested by French-wide study of oncogenic small ruminant β-retrovirus diversity.

Introduction: ENTV (Enzootic Nasal Tumor Virus) and JSRV (Jaagsiekte Sheep Retrovirus) are β-retroviruses responsible for respiratory cancers in sheep and goats. In this study, we analyzed the genetic features of the sheep and goat β-Retroviruses (29 JSRV and 24 ENTV strains) circulating in France to identify molecular signatures associated with disease severity in flocks.

Methods: We developed a highly specific PCR to amplify and sequence exogenous targeted regions or near full length proviruses based on limited discriminating motifs along their genomes.

Perspectives of parents with lived experience of cytomegalovirus infection, on universal newborn screening for congenital cytomegalovirus (cCMV) in Canada: a patient-led qualitative study.

Objective: To understand parental perspectives regarding universal newborn screening (UNS) for congenital cytomegalovirus (cCMV) in Canada.

Design: A qualitative, patient-led study using the Patient and Community Engagement Research approach consisting of online focus groups and in-depth individual interviews to understand parental preferences regarding UNS for cCMV. Data were analysed iteratively using inductive thematic analysis and narrative story analysis.

Functional decline, long term symptoms and course of frailty at 3-months follow-up in COVID-19 older survivors, a prospective observational cohort study.

Background: Aging is one of the most important prognostic factors increasing the risk of clinical severity and mortality of COVID-19 infection. However, among patients over 75 years, little is known about post-acute functional decline.

Objective: The aim of this study was to identify factors associated with functional decline 3 months after COVID-19 onset, to identify long term COVID-19 symptoms and transitions between frailty statesafter COVID-19 onset in older hospitalized patients.

Tuberous sclerosis complex for the pulmonologist.

Tuberous sclerosis complex (TSC) is a rare multisystem genetic disorder affecting almost all organs with no sex predominance. TSC has an autosomal-dominant inheritance and is caused by a heterozygous mutation in either the or gene leading to hyperactivation of the mammalian target of rapamycin (mTOR). TSC is associated with several pulmonary manifestations including lymphangioleiomyomatosis (LAM), multifocal micronodular pneumocyte hyperplasia (MMPH) and chylous effusions.

Evidence of jaagsiekte sheep retrovirus-induced pulmonary adenocarcinoma in Ouled Djellal breed sheep in Algeria.

We report the occurrence of lung cancer in a six months old lamb of Ouled Djellal breed from Algeria. The main clinical sign was a considerable amount of whitish foamy fluid discharge from the nostrils when the animal head was lowered and the rear end was lifted. The post-mortem examination revealed the presence of enlarged, heavy and edematous lungs with diffuse or foci areas, reddish or white-gray in color.

Remodeling of the Actin Network Associated with the Non-Structural Protein 1 (NS1) of West Nile Virus and Formation of NS1-Containing Tunneling Nanotubes.

The cellular response to the recombinant NS1 protein of West Nile virus (NS1) was studied using three different cell types: Vero E6 simian epithelial cells, SH-SY5Y human neuroblastoma cells, and U-87MG human astrocytoma cells. Cells were exposed to two different forms of NS1: (i) the exogenous secreted form, sNS1, added to the extracellular milieu; and (ii) the endogenous NS1, the intracellular form expressed in plasmid-transfected cells. The cell attachment and uptake of sNS1 varied with the cell type and were only detectable in Vero E6 and SH-SY5Y cells.

Activation of the mTOR/ Akt pathway in thymic epithelial cells derived from thymomas.

The pathogenesis of thymic epithelial tumors remains poorly elucidated. The PIK3/Akt/mTOR pathway plays a key role in various cancers; interestingly, several phase I/II studies have reported a positive effect of mTOR inhibitors in disease control in thymoma patients. A major limit for deciphering cellular and molecular events leading to the transformation of thymic epithelial cells or for testing drug candidates is the lack of reliable in vitro cell system.

Dysregulation of the endothelin pathway in lymphangioleiomyomatosis with no direct effect on cell proliferation and migration.

LAM is a rare low-grade metastasizing lung neoplasm. Inhibitors of mTOR improve clinical outcome of LAM patients by preventing loss of lung function. Nevertheless, other cell targets may be of interest for drug development.

First case report of enzootic nasal adenocarcinoma in "Ouled Djellal" ewe in Algeria.

We report clinical and pathological features of enzootic nasal adenocarcinoma (ENA) in one sheep in Algeria. A one-year-old Ouled Djellal sheep from a large herd (~1240 animals), located in Bordj Bou Arreridj, Algeria, was clinically diagnosed by the presence of persistent seromucous nasal discharge, head shaking, muzzle licking, dyspnoea, exophthalmia and frontal protrusion. The sheep was euthanized, and the necropsy was performed.

Blocked expression of key genes of the angiogenic pathway in JSRV-induced pulmonary adenocarcinomas.

JSRV (Jaagsiekte Sheep Retrovirus) is a retrovirus inducing a transmissible lung adenocarcinoma in sheep and goats with predominantly lepidic and papillary lesions. This naturally occurring lung cancer in large animals shares many features with human pneumonic-type lung adenocarcinomas with predominant lepidic growth. The metastatic spread is rare in both human and animal cancers.

Intra-Thoracic Chemo-Hyperthermia for pleural recurrence of thymoma.

Background: Pleural recurrences are a hallmark of thymomas, and represent a challenge for multidisciplinary management. The purpose of this study was to assess the feasibility and the results in terms of morbidity, mortality and survival rates, of Intra-Thoracic Chemo-Hyperthermia (ITCH) for the treatment of pleural recurrences of thymomas.

Methods: Retrospective analysis of 19 consecutives patients between 1997 and 2015 treated by surgical cytoreduction (pleurectomy) followed by ITCH with 25mg/m of mitomycin, and 50mg/m of Cisplatin.

Characterization of a novel canine T-cell line established from a spontaneously occurring aggressive T-cell lymphoma with large granular cell morphology.

Dogs with lymphoma are established as good model for human non-Hodgkin lymphoma studies. Canine cell lines derived from lymphomas may be valuable tools for testing new therapeutic drugs. In this context, we established a canine T-cell line, PER-VAS, from a primary aggressive T-cell lymphoma with large granular morphology.

Early Steps of Jaagsiekte Sheep Retrovirus-Mediated Cell Transformation Involve the Interaction between Env and the RALBP1 Cellular Protein.

Unlabelled: Ovine pulmonary adenocarcinoma is a naturally occurring lung cancer in sheep induced by the Jaagsiekte sheep retrovirus (JSRV). Its envelope glycoprotein (Env) carries oncogenic properties, and its expression is sufficient to induce in vitro cell transformation and in vivo lung adenocarcinoma. The identification of cellular partners of the JSRV envelope remains crucial for deciphering mechanisms leading to cell transformation.

Interstitial lung disease associated with Equine Infectious Anemia Virus infection in horses.

EIA (Equine Infectious Anemia) is a blood-borne disease primarily transmitted by haematophagous insects or needle punctures. Other routes of transmission have been poorly explored. We evaluated the potential of EIAV (Equine Infectious Anemia Virus) to induce pulmonary lesions in naturally infected equids.

Lung progenitors from lambs can differentiate into specialized alveolar or bronchiolar epithelial cells.

Background: Airways progenitors may be involved in embryogenesis and lung repair. The characterization of these important populations may enable development of new therapeutics to treat acute or chronic lung disease. In this study, we aimed to establish the presence of bronchioloalveolar progenitors in ovine lungs and to characterize their potential to differentiate into specialized cells.

Copy number variation and differential expression of a protective endogenous retrovirus in sheep.

The Jaagsiekte sheep retrovirus exJSRV and its endogenous counterpart enJSRV co-exist in sheep. exJSRV, a betaretrovirus, is the etiological agent of ovine pulmonary adenocarcinoma, and it has been demonstrated in vitro that an enJSRV Gag variant bearing the R-to-W amino acid change at position 21 was able to block exJSRV budding from the cells, providing a potential protective role for the host. In this work, we developed a fast mutation detection assay based on the oligo ligation assay (OLA) that permits the quantification of the relative proportions of the R21 and W21 Gag variants present in individual genomes and in cDNA obtained from normal and exJSRV-induced lung tumors.

Professional exposure to goats increases the risk of pneumonic-type lung adenocarcinoma: results of the IFCT-0504-Epidemio study.

Pneumonic-type lung adenocarcinoma (P-ADC) represents a distinct subset of lung cancer with specific clinical, radiological, and pathological features. Given the weak association with tobacco-smoking and the striking similarities with jaagsiekte sheep retrovirus (JSRV)-induced ovine pulmonary adenocarcinoma, it has been suggested that a zoonotic viral agent infecting pulmonary cells may predispose to P-ADC in humans. Our objective was to explore whether exposure to domestic small ruminants may represent a risk factor for P-ADC.

Oxidant-antioxidant imbalance in horses infected with equine infectious anaemia virus.

This study assesses the impact of equine infectious anaemia virus (EIAV) infection on the oxidant/antioxidant equilibrium of horses. Blood samples from 96 Romanian horses aged 1-25 years, were divided into different groups according to their EIAV-infection status, age, and time post-seroconversion. The effect of infection on oxidative stress was estimated by measuring enzymatic antioxidants (superoxide dismutase [SOD], glutathione peroxidase [GPx] and catalase), non-enzymatic antioxidants (uric acid and carotenoids), and lipid peroxidation (malondialdehyde [MDA]).

SRLVs: a genetic continuum of lentiviral species in sheep and goats with cumulative evidence of cross species transmission.

Lentiviruses from distinct animal species have in common their genomic organization, the induction of slowly progressive diseases over months or years, the large spectrum of induced symptoms and concerned organs, the frequent inapparent infection without any detectable clinical signs, their ability to persist into their hosts despite an often strong and mature immune response. Lentiviruses are also characterized by their genomic plasticity and the rapid evolution of the viral species. SRLVs infecting goats and sheep follow a genomic evolution pattern similar to that observed in HIV or in other lentiviruses.

Small ruminant lentivirus proviral sequences from wild ibexes in contact with domestic goats.

Small ruminant lentiviruses (SRLV) are widespread amongst domesticated goats and sheep worldwide, but have not been clearly identified in wild small ruminants, where they might constitute an animal health risk through contamination from local domesticates. SRLV proviruses from three ibexes from the French Alps are described and sequences from their gag gene and long terminal repeats (LTRs) were compared with sequences from local goats and goat/ibex hybrids. The ibex and hybrid proviruses formed a closely related group with <2 % nucleotide difference.

A large animal model to evaluate the effects of Hsp90 inhibitors for the treatment of lung adenocarcinoma.

Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung cancer of sheep caused by Jaagsiekte sheep retrovirus (JSRV). The JSRV envelope glycoprotein (Env) functions as a dominant oncoprotein in vitro and in vivo. In order to develop the basis for the use of OPA as a lung cancer model, we screened a variety of signal transduction inhibitors for their ability to block transformation by the JSRV Env.

Toll-like receptor 3 (TLR3): a new marker of canine monocytes-derived dendritic cells (cMo-DC).

Toll-like receptors (TLRs) are a family of functionally important receptors for recognition of pathogen-associated molecular pattern (PAMP) since they trigger the pro-inflammatory response and upregulation of costimulatory molecules, linking the rapid innate response to adaptative immunity. In human leukocytes, TLR3 has been found to be specifically expressed in dendritic cells (DC). This study examined the expression of TLR3 in canine monocytes-derived DC (cMo-DC) and PBMC using three new anti-TLR3 mAbs (619F7, 722E2 and 713E4 clones).

In silico segmentations of lentivirus envelope sequences.

Background: The gene encoding the envelope of lentiviruses exhibits a considerable plasticity, particularly the region which encodes the surface (SU) glycoprotein. Interestingly, mutations do not appear uniformly along the sequence of SU, but they are clustered in restricted areas, called variable (V) regions, which are interspersed with relatively more stable regions, called constant (C) regions. We look for specific signatures of C/V regions, using hidden Markov models constructed with SU sequences of the equine, human, small ruminant and simian lentiviruses.

Jaagsiekte Sheep Retrovirus (JSRV): from virus to lung cancer in sheep.

Jaagsiekte Sheep Retrovirus (JSRV) is a betaretrovirus infecting sheep. This virus is responsible for a pulmonary adenocarcinoma, by transformation of epithelial cells from the bronchioli and alveoli. This animal cancer is similar to human bronchioloalveolar cancer (BAC), a specific form of human lung cancer for which a viral aetiology has not yet been identified.

Alveolar type II cells isolated from pulmonary adenocarcinoma: a model for JSRV expression in vitro.

Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring cancer in sheep, with clinical, radiologic, and histopathologic features similar to that of human pneumonic-type bronchioloalveolar carcinoma. JSRV (Jaagsiekte Sheep RetroVirus) is the etiologic agent of this contagious lung cancer in sheep. Cells involved in the tumor derive from alveolar type II cells and Clara cells, epithelial cells of the distal respiratory tract.