Papillary meningioma with multifocal leptomeningeal spread in a dog

An 11-year-old, English cocker spaniel was presented with subacute progressive signs of vestibular ataxia, tetraparesis, left-sided proprioceptive deficits, positional ventrolateral strabismus of the right eye and a right-sided menace deficit. Magnetic resonance imaging of the cranium and cranial cervical spinal cord revealed multifocal T2 hyper-/T1-hypointense intradural lesions with dural tail signs and intra-axial and intramedullary extension. Medical treatment resulted in initial improvement before deterioration was noticed. Cytological examination results of computed tomography-guided fine-needle aspiration biopsy of the C1–C2 lesion were consistent with mesenchymal neoplasia. Three days later, after progressive clinical deterioration, euthanasia was performed. Postmortem examination and subsequent histological examination of the brainstem and spinal cord revealed multifocal, strongly infiltrative growth of neoplastic cells with areas of pseudo-rosette formation by cylindrical neoplastic cells with moderately large, oval nuclei in addition to areas of spindle-shaped neoplastic cells with meningothelial whorls. The final diagnosis was a papillary (grade III) meningioma with multifocal leptomeningeal spread

Pathological findings in stranded harbor porpoises (Phocoena phocoena) with special focus on anthropogenic causes

Humans impact natural systems at an unprecedented rate. The North Sea is one of the regions in the world with the highest levels of anthropogenic activity. Here, the harbor porpoise (Phocoena phocoena) is an abundant species and is often regarded as an ecosystem sentinel. A post-mortem surveillance program was established in the Netherlands aimed at increasing knowledge of the effects of human activities on harbor porpoises. In this study, we describe the pathological findings related to anthropogenic and natural causes of death categories in 612 harbor porpoises that stranded between 2008 and 2019, and assess their relations to age, sex, season, and location. The largest anthropogenic category was bycatch (17%), with mainly juveniles affected and peak periods in March and September–October. Other, infrequently diagnosed anthropogenic causes of death were trauma (4%), largely most likely due to ship collisions, and marine debris ingestion and entanglement (0.3%). The risk of dying from anthropogenic causes was highest for juveniles. Lesions compatible with noise-induced hearing loss were investigated in carcasses which were fresh enough to do so (n = 50), with lesions apparent in two porpoises. Non-direct human-induced threats included infectious diseases, which were by far the largest cause of death category (32%), and affected mainly adults. Also, gray seal (Halichoerus grypus) attacks were a frequently assigned cause of death category (24%). There were more acute predation cases in the earlier study years, while porpoises with lesions that suggested escape from gray seal attacks were diagnosed more recently, which could suggest that porpoises adapted to this threat. Our study contributes to understanding porpoise health in response to persisting, new, emerging, and cumulative threats. Building up such knowledge is crucial for conservation management of this protected species

Multi-omics approach identifies germline regulatory variants associated with hematopoietic malignancies in retriever dog breeds

Histiocytic sarcoma is an aggressive hematopoietic malignancy of mature tissue histiocytes with a poorly understood etiology in humans. A histologically and clinically similar counterpart affects flat-coated retrievers (FCRs) at unusually high frequency, with 20% developing the lethal disease. The similar clinical presentation combined with the closed population structure of dogs, leading to high genetic homogeneity, makes dogs an excellent model for genetic studies of cancer susceptibility. To determine the genetic risk factors underlying histiocytic sarcoma in FCRs, we conducted multiple genome-wide association studies (GWASs), identifying two loci that confer significant risk on canine chromosomes (CFA) 5 (Pwald = 4.83x10-9) and 19 (Pwald = 2.25x10-7). We subsequently undertook a multi-omics approach that has been largely unexplored in the canine model to interrogate these regions, generating whole genome, transcriptome, and chromatin immunoprecipitation sequencing. These data highlight the PI3K pathway gene PIK3R6 on CFA5, and proximal candidate regulatory variants that are strongly associated with histiocytic sarcoma and predicted to impact transcription factor binding. The CFA5 association colocalizes with susceptibility loci for two hematopoietic malignancies, hemangiosarcoma and B-cell lymphoma, in the closely related golden retriever breed, revealing the risk contribution this single locus makes to multiple hematological cancers. By comparison, the CFA19 locus is unique to the FCR and harbors risk alleles associated with upregulation of TNFAIP6, which itself affects cell migration and metastasis. Together, these loci explain ~35% of disease risk, an exceptionally high value that demonstrates the advantages of domestic dogs for complex trait mapping and genetic studies of cancer susceptibility

Progressive retrocorneal pigmentation in dogs: A clinical report of 34 cases

OBJECTIVES: To describe the signalment, ophthalmic examination findings, and follow-up of dogs affected with a previously unreported retrocorneal pigmentary lesion. MATERIALS AND METHODS: Retrospective record evaluation spanning 2009-2019. RESULTS: Retrocorneal pigmentary lesions were described in 34 patients (46 eyes). German Shepherds (n = 7), Jack Russel terriers (n = 5), and terrier crosses (n = 4) made up 16/34 (47.1%) of the cases. The mean age was 13.5 years (range 1.4-14.2 years), and 16/30 (53.3%) dogs were female. Most dogs were affected unilaterally (22/34 (64.7%)), the others bilaterally, and 5/34 (14.7%) were referred for it while the others were incidentally diagnosed. The lesions affected the ventral, peripheral, inner cornea and had a round/undulated leading edge. The number of corneal clock hours affected was known for 41/46 (89.1%) eyes and involved 1-3 clock hours in 32/41 (78.1%) eyes, 4-6 in 6/41 (14.6%), 7-9 in 2/41 (4.9%), and 10 in 1/41 (2.4%). The central cornea was affected in 9/46 (19.6%) eyes, and in 5/9 (55.6%), the median corneal clarity score was G2 (scale: G0-G4). The commonest additional findings included free-floating uveal cysts (11/34 dogs, 32.4%), cataracts (6/34 dogs, 17.6%), and primary glaucoma (5/34 dogs, 14.7%). Gonioscopy was available in 16/34 (47.1%) dogs and was normal except in primary glaucoma cases. Follow-up was documented in 13/34 (38.2%) dogs with a mean follow-up of 17 months (range: 5-26 months). Lesion progression was documented in 6/13 (46.2%) dogs. CONCLUSIONS: Retrocorneal pigmentation occurs as a slowly progressive lesion of older dogs that could impact vision. Histological studies of affected eyes are warranted

Antiviral activity of selected cathelicidins against infectious bronchitis virus

Avian infectious bronchitis (IB) is a highly contagious disease caused by infectious bronchitis virus (IBV), a coronavirus of domestic fowl. IB is a major concern in the poultry industry, causing worldwide economic losses through decreased egg production and quality and by increasing the chicken's susceptibility for secondary bacterial infections, particularly Escherichia coli. In this study, the anti-IBV activity of cathelicidins, small antimicrobial peptides of the innate immune system was investigated. The cell culture adapted (nonvirulent) IBV strain Beaudette was effectively inhibited by the human cathelicidin LL-37 in bovine hamster kidney-21 cells at nontoxic concentrations. The peptide needed to be present during virus inoculation to effectively inhibit the infection of IBV-Beaudette, indicating that LL-37 likely bound viral particles. However, no clear morphological changes in the IBV virion upon binding were observed by electron microscopy. In this cell culture model, chicken cathelicidins (CATH1-3) were inactive against IBV-Beaudette. In contrast, in multicellular infection models using the virulent IBV-M41 strain the activities of human and chicken cathelicidins were different. In particular, upon inoculation of 10-day-old embryonic eggs with IBV-M41, CATH-2 reduced the viral load to a higher extend than LL-37. Similarly, viral infection of chicken tracheal organ cultures with IBV-M41 was significantly reduced in the presence of CATH-2 but not LL-37. These results indicate a potential antiviral role for CATH-2 upon IBV infection in vivo

Redirecting coronavirus to a nonnative receptor through a virus-encoded targeting adapter

Murine hepatitis coronavirus (MHV)-A59 infection depends on the interaction of its spike (S) protein with the cellular receptor mCEACAM1a present on murine cells. Human cells lack this receptor and are therefore not susceptible to MHV. Specific alleviation of the tropism barrier by redirecting MHV to a tumor-specific receptor could lead to a virus with appealing properties for tumor therapy. To demonstrate that MHV can be retargeted to a nonnative receptor on human cells, we produced bispecific adapter proteins composed of the N-terminal D1 domain of mCEACAM1a linked to a short targeting peptide, the six-amino-acid His tag. Preincubation of MHV with the adapter proteins and subsequent inoculation of human cells expressing an artificial His receptor resulted in infection of these otherwise nonsusceptible cells and led to subsequent production of progeny virus. To generate a self-targeted virus able to establish multiround infection of the target cells, we subsequently incorporated the gene encoding the bispecific adapter protein as an additional expression cassette into the MHV genome through targeted RNA recombination. When inoculated onto murine LR7 cells, the resulting recombinant virus indeed expressed the adapter protein. Furthermore, inoculation of human target cells with the virus resulted in a His receptor-specific infection that was multiround. Extensive cell-cell fusion and rapid cell killing of infected target cells was observed. Our results show that MHV can be genetically redirected via adapters composed of the S protein binding part of mCEACAM1a and a targeting peptide recognizing a nonnative receptor expressed on human cells, consequently leading to rapid cell death. The results provide interesting leads for further investigations of the use of coronaviruses as antitumor agents

The avian coronavirus spike protein

Avian coronaviruses of the genus Gammacoronavirus are represented by infectious bronchitis virus (IBV), the coronavirus of chicken. IBV causes a highly contagious disease affecting the respiratory tract and, depending on the strain, other tissues including the reproductive and urogenital tract. The control of IBV in the field is hampered by the many different strains circulating worldwide and the limited protection across strains due to serotype diversity. This diversity is believed to be due to the amino acid variation in the S1 domain of the major viral attachment protein spike. In the last years, much effort has been undertaken to address the role of the avian coronavirus spike protein in the various steps of the virus' live cycle. Various models have successfully been developed to elucidate the contribution of the spike in binding of the virus to cells, entry of cell culture cells and organ explants, and the in vivo tropism and pathogenesis. This review will give an overview of the literature on avian coronavirus spike proteins with particular focus on our recent studies on binding of recombinant soluble spike protein to chicken tissues. With this, we aim to summarize the current understanding on the avian coronavirus spike's contribution to host and tissue predilections, pathogenesis, as well as its role in therapeutic and protective interventions