Comparative Neuropathogenesis of Equine Herpesvirus 9 and its Mutant Clone (SP21) Inoculated Intranasally in a Hamster Model.

The neuropathogenesis of equine herpesvirus 9 (EHV-9), a neurotropic herpesvirus, and its mutant clone (SP21) was studied experimentally in a hamster model. EHV-9-infected hamsters showed clinical signs of infection at 3 days post infection (dpi), while infection with SP21 resulted in clinical signs at 4 dpi. Clinical signs were more severe in the EHV-9-infected group than in the SP21-infected group. There was a significant difference in the time of anterograde transmission of EHV-9 and SP21 inside the brain. Viraemia was detected in the EHV-9-infected group at 4-5 dpi, while no viraemia was detected in the SP21-infected group. The serum concentration of tumour necrosis factor-α was significantly higher in EHV-9-infected animals than in those infected by SP21 group at 4-5 dpi, but there was no difference in the serum concentration of interferon-γ. The spatiotemporal profiles of viral replication and virus-associated histopathology were remarkably similar, were high in the olfactory bulb and cerebral hemispheres, and decreased progressively towards the medulla oblongata. The mean group scores of the histopathological changes for the entire brain were significantly higher in the EHV-9 group than in the SP21 group at all time points, starting from 3 dpi. These results suggest that the gene products of the open reading frame (ORF)19 and ORF14 play essential roles in the neuropathogenesis of EHV-9, as the two point-mutations detected in SP21 significantly altered the neuropathogenesis of the virus.

Overexpression of Peroxiredoxin 6 Protects Neoplastic Cells against Apoptosis in Canine Haemangiosarcoma.

Canine haemangiosarcoma (HSA), like human angiosarcoma, is an uncommon malignant vascular endothelial cell tumour associated with a poor prognosis. The peroxiredoxin (PRDX) family of peroxidases, which comprises six members in mammals (PRDX1-6), might contribute to cancer cell survival in the face of oxidative stress as these proteins exhibit frequent upregulation in cancer cells. In this study, we investigated the expression levels of PRDX6 in spontaneously arising primary canine HSAs by immunohistochemical analysis, identifying marked expression of this protein. Both PRDX6 mRNA and protein were overexpressed in HSA cell lines compared with normal canine endothelial cells, although some variation was observed between the different HSA cell lines. Small interfering RNA-induced downregulation of PRDX6 promoted apoptosis in the HSA cell lines. The observation that PRDX6 suppression increased the cytotoxicity of these cells suggests that PRDX6 might play an important cytoprotective role.

Immunohistochemical analysis of CD146 expression in canine skin tumours.

CD146, a cell adhesion molecule, is overexpressed in a variety of carcinomas, including melanoma, prostate cancer, epithelial ovarian cancer, and breast cancer. The level of expression is directly correlated with tumour progression and metastatic potential. The most commonly affected organ for both neoplastic and non-neoplastic tumours is the skin. The objective of this study is to investigate the immunohistochemical expression of CD146 in canine skin tumours of epidermal or follicular origin in 53 squamous cell carcinomas (SCCs), 9 squamous papillomas, 7 infundibular keratinizing acanthomas (IKA), 21 trichoepitheliomas, 13 trichoblastomas, and 3 pilomatricomas. Immunohistochemical results showed that SCCs (90.6%), squamous papilloma (33.3%), IKA (85.7%), trichoepithelioma (85.9%), trichoblastoma (30.8%) and pilomatricoma (100%), respectively, were positive for CD146. The significant expression of CD146 in SCCs supports its importance as a useful treatment target. CD146 could also be used in differentiation of trichoepithelioma and trichoblastoma.

Immunohistochemical Detection of Urokinase Plasminogen Activator and Urokinase Plasminogen Activator Receptor in Canine Vascular Endothelial Tumours.

Immunohistochemistry was used to assess the expression of urokinase plasminogen activator (uPA) and uPA receptor (uPAR) in 57 canine primary haemangiosarcomas (HSAs), 26 canine cutaneous haemangiomas (HAs) and in control sections of canine cutaneous granulation tissue. The correlation between uPA/uPAR expression and the Ki67 labelling index (LI) was estimated in the HSA and HA tissues. uPA was expressed by 73.2% and 75.0% of splenic HSAs and non-splenic HSAs, respectively. All HSA tissues tested expressed uPAR. Expression of both molecules was significantly higher in HSAs than in cutaneous HAs (3.8% for uPA and 30.7% for uPAR). The average Ki67 LI of the uPA(+)/uPAR(+) HSAs was significantly higher than that of uPA(-)/uPAR(+) HSAs and HA tissues (mean ± SDs 32.8 ± 15.3, 15.2 ± 7.2 and 2.1 ± 0.7, respectively; P <0.05). These results suggest that uPA and uPAR play a significant role in the malignant proliferation of canine HSA, regardless of the primary origin of the tumour.