ORF virus causes tumor-promoting inflammation in sheep and goats.

ORF virus (ORFV) causes contagious ecthyma ("ORF"), a disease of sheep and goats characterized by lesions ranging from vesicles and pustules to atypical papilloma-like and angiomatous lesions in the skin and mucosae. The authors investigated the molecular factors leading to the ORF-associated atypical tumor-like changes. Fifteen lambs, 15 kids, and an adult ram clinically affected by natural ORFV infection were enrolled in the study and examined by several methods. ORFV was detected by viral culture or real-time polymerase chain reaction (RT-PCR) in the lesioned tissues and in the blood of the clinically affected sheep and goats. Surprisingly, ORFV was also detected in the blood of healthy goats from an affected herd. Microscopically, they found a pseudo-papillomatous proliferation of the epithelium, while the dermis and lamina propria were expanded by a proliferating neovascular component that highly expressed the viral vascular endothelial growth factor (vVEGF) and its host receptor vascular endothelial growth factor receptor 2 (VEGFR2). Immunohistochemistry, immunofluorescence, and in situ hybridization for mRNA showed that epidermal growth factor receptor (EGFR) was expressed in the fibrovascular component, in the infiltrating CD163+ macrophages, and in the basal stratum of the epidermis. Confocal immunofluorescence microscopy demonstrated that CD163+ macrophages were associated with VEGF and VEGFR2. Finally, they found by quantitative RT-PCR the overexpression of the interleukin-6 and VEGFR2 genes in the lesioned tissues. These findings suggest that ORFV activates an inflammatory reaction characterized by CD163+ macrophages expressing EGFR and VEGFR2, which might play an oncogenic role through synergistic action with vVEGF signaling.

Malignant Catarrhal Fever in Sardinia (Italy): A Case Report.

Using a multidisciplinary approach, this report describes a clinical case of malignant catarrhal fever (MCF) occurring in a calf, which shared the pasture with sheep on a farm located in the island of Sardinia (Italy). We confirmed the conventional clinico-histopathological features of MCF, as well was the presence of Ovine herpesvirus type 2 (OvHV-2) DNA in several tissues, employing histological and virological investigations. The phylogenetic analysis revealed that this Sardinian OvHV-2 strain is genetically similar to all the other Italian strains. By Real Time PCR examinations of blood samples collected across Sardinia's sheep population, which is considered the most important reservoir species, we discovered an OvHV-2 prevalence ranging from 20 to 30 percent. Despite the high prevalence of OvHV-2 in the Sardinian sheep population, clinical disease in bovine remains sporadic; further investigations are needed to understand the risk factors that regulate this epidemiological aspect.

Association of N176K and L141F dimorphisms of the PRNP gene with lack of pathological prion protein deposition in placentas of naturally and experimentally scrapie-affected ARQ/ARQ sheep.

The placenta is important in the horizontal transmission of the aetiological agent in scrapie-affected sheep. It has been demonstrated that the placentas of fetuses carrying the dimorphism Q171R of the PRNP gene is resistant to pathological prion protein (PrP(Sc)) accumulation in the placenta. To test whether other PRNP polymorphisms are associated with a lack of placental PrP(Sc) deposition, we carried out a study on 26 naturally and 11 experimentally scrapie-affected ewes with or without clinical signs. PrP(Sc) was detected in the placenta of ARQ/ARQ(wild type) fetuses by Western blot and immunohistochemical analysis, but not in ARQN(176)/ARQK(176) or, as expected, ARQ/ARR samples. Furthermore, three of four AL(141)RQ/AF(141)RQ placentas were also PrP(Sc) negative, suggesting that the dimorphism at codon 141 may also mediate placental deposition of PrP(Sc). This finding demonstrates for the first time that fetal PRNP polymorphisms, other than those at codon 171, are associated with the lack of placental deposition of PrP(Sc).

Pathological findings in a Dachshund-cross dog with neuroaxonal dystrophy.

BACKGROUND: Neuroaxonal dystrophy (NAD) is a neurodegenerative condition affecting humans and animals characterized by the widespread presence of swollen axons (spheroids). CASE PRESENTATION: Herein, we report the pathological findings in a case of neuroaxonal dystrophy in a Dachshund-cross puppy, which was euthanized because of a proprioceptive positioning deficits and irreversible ataxia of the hind limbs. Histologically, there was a bilaterally symmetric neuroaxonal dystrophy with eosinophilic axonal spheroids exclusively localized at the level of the ventral posterior lateral nucleus of the thalamus, medial lemniscus, gracilis nucleus, medial cuneatus nucleus in the brain as well as the gracilis and cuneatus fasciculi throughout the spinal cord. CONCLUSION: To the authors' knowledge, this is the first report of canine neuroaxonal dystrophy with this exclusive and specific localization only in the neuronal circuit implicated in the transmission of conscious proprioceptive information.

Glioblastoma with oligodendroglioma component in a ewe.

Herein we describe a glioblastoma partially occupying the telencephalic portion of the left cerebral hemisphere of a Sardinian (syn. Sarda) breed ewe. Microscopically, the mass consisted of a pleomorphic spindle-shaped cell component organized as bundles and numerous small areas of round cells displaying an oligodendroglioma-like aspect. A high number of mitotic figures, large areas of necrosis surrounded by pseudopalisading glial cells, and multiple foci of dystrophic mineralization were also observed. The neoplasm was highly vascularized with glomerular vascular proliferation. Immunohistochemically, neoplastic cells proved to be strongly positive for nestin, vimentin, and olig-2, whereas they were invariably negative for synaptophysin. Few neoplastic cells and reactive astrocytes, mainly located at the edge of necrotic foci, proved to be positive for glial fibrillary acidic protein, whereas glomerular vascular proliferation was clearly positive for factor VIII and vascular endothelial growth factor. Gene sequencing analysis demonstrated homozygous p53 tumor suppressor gene (TP53) point mutations in the DNA-binding domain located in exon 8. The presence of round cells immunoreactive for olig-2 demonstrated that this tumor is a glioblastoma with oligodendroglioma component. Our pathologic, immunohistochemical, and molecular findings largely overlap those previously reported in humans and dogs.