Interferon-Stimulated Genes-Mediators of the Innate Immune Response during Canine Distemper Virus Infection.

The demyelinating canine distemper virus (CDV)-leukoencephalitis represents a translational animal model for multiple sclerosis. The present study investigated the expression of type I interferon (IFN-I) pathway members in CDV-induced cerebellar lesions to gain an insight into their role in lesion development. Gene expression of 110 manually selected genes in acute, subacute and chronic lesions was analyzed using pre-existing microarray data. Interferon regulatory factor (IRF) 3, IRF7, signal transducer and activator of transcription (STAT) 1, STAT2, MX protein, protein kinase R (PKR), 2'-5'-oligoadenylate synthetase (OAS) 1 and interferon-stimulated gene (ISG) 15 expression were also evaluated using immunohistochemistry. Cellular origin of STAT1, STAT2, MX and PKR were determined using immunofluorescence. CDV infection caused an increased expression of the antiviral effector proteins MX, PKR, OAS1 and ISG15, which probably contributed to a restricted viral replication, particularly in neurons and oligodendrocytes. This increase might be partly mediated by IRF-dependent pathways due to the lack of changes in IFN-I levels and absence of STAT2 in astrocytes. Nevertheless, activated microglia/macrophages showed a strong expression of STAT1, STAT2 and MX proteins in later stages of the disease, indicating a strong activation of the IFN-I signaling cascade, which might be involved in the aggravation of bystander demyelination.

A de Novo EDA-Variant in a Litter of Shorthaired Standard Dachshunds with X-Linked Hypohidrotic Ectodermal Dysplasia.

In this study, we present a detailed phenotype description and genetic elucidation of the first case of X-linked hypohidrotic ectodermal dysplasia in the shorthaired standard Dachshund. This condition is characterized by partial congenital hypotrichosis, missing and malformed teeth and a lack of eccrine sweat glands. Clinical signs including dental radiographs and histopathological findings were consistent with ectodermal dysplasia. Pedigree analysis supported an X-recessive mode of inheritance. Whole-genome sequencing of one affected puppy and his dam identified a 1-basepair deletion within the ectodysplasin-A (EDA) gene (CM000039.3:g.54509504delT, c.458delT). Sanger sequencing of further family members confirmed the EDA:c.458delT-variant. Validation in all available family members, 37 unrelated shorthaired standard Dachshunds, 128 further Dachshunds from all other coat and size varieties and samples from 34 dog breeds revealed the EDA:c.458delT-variant to be private for this family. Two heterozygous females showed very mild congenital hypotrichosis but normal dentition. Since the dam is demonstrably the only heterozygous animal in the ancestry of the affected animals, we assume that the EDA:c.458delT-variant arose in the germline of the granddam or in an early embryonic stage of the dam. In conclusion, we detected a very recent de-novo EDA mutation causing X-linked hypohidrotic ectodermal dysplasia in the shorthaired standard Dachshund.

Association of Batai Virus Infection and Encephalitis in Harbor Seals, Germany, 2016.

We isolated Batai virus from the brain of a euthanized, 26-year-old, captive harbor seal with meningoencephalomyelitis in Germany. We provide evidence that this orthobunyavirus can naturally infect the central nervous system of a mammal. The full-genome sequence showed differences from a previously reported virus isolate from a mosquito in Germany.

Subcutaneous merocercoids of Clistobothrium sp. in two Cape fur seals (Arctocephalus pusillus pusillus).

Fur seals represent intermediate hosts of the cestode Clistobothrium. Large sharks are definitive hosts for these parasites. Two female, 25- and 27-year-old fur seals, caught in the 1980s at the South African coast, were examined pathomorphologically. Both animals showed multifocal, up to 1 cm in diameter large cavities of the thoracic and abdominal subcutaneous adipose tissue containing intraluminal metacestodes of tapeworms, which were surrounded by a locally extensive, pyogranulomatous panniculitis. The metacestodes (merocercoids) of one fur seal were isolated from the subcutaneous adipose tissue and characterized morphologically and for the first time from this host by molecular techniques. The morphometric data corresponded with 'delphini'-morphotype merocercoids, but the sequence of the partial 28S ribosomal RNA gene identified them as conspecific with merocercoids of the morphotype 'grimaldii'. These merocercoid types are morphologically Type XV metacestodes of marine tapeworms and represent different species of Clistobothrium. Sequence data were generated for 18S, ITS1, 5.8S, ITS2, partial 28S ribosomal DNA and partial mitochondrial cox1 gene and phylogenetic analysis of 18S rRNA and partial 28S rRNA genes identified the fur seal merocercoids as Clistobothrium species. However, it cannot yet be assigned to species level because of limited molecular data from adult stages. Most likely, both fur seals were infected as juveniles in their original habitat, the coastal regions of South Africa. The metacestode infection is probably an incidental finding, however, there is a chronic inflammatory reaction next to the subcutaneous merocercoids. It is noteworthy, that the merocercoids remain in a potentially infective stage even after more than 20 years.

Mycobacterium avium subsp. hominissuis Infection in a Domestic Rabbit, Germany.

Mycobacterium avium subsp. hominissuis is an opportunistic pathogen present in soil and dust. We report M. avium subsp. hominissuis infection found in a domestic rabbit in Hannover, Germany, in May 2017.

Type I interferons in the pathogenesis and treatment of canine diseases.

Type I interferons (IFNs) such as IFN-α, IFN-ß, IFN-ε, IFN-κ, and IFN-ω represent cytokines, which are deeply involved in the regulation and activation of innate and adaptive immune responses. They possess strong antiviral, antiproliferative, and immunomodulatory activities allowing their use in the therapy of different viral diseases, neoplasms, and immune-mediated disorders, respectively. Initially, treatment strategies were based on nonspecific inducers of type I IFNs, which were soon replaced by different recombinant proteins. Drugs with type I IFNs as active agents are currently used in the treatment of hepatitis B and C virus infection, lymphoma, myeloid leukemia, renal carcinoma, malignant melanoma, and multiple sclerosis in humans. In addition, recombinant feline IFN-ω has been approved for the treatment of canine parvovirus, feline leukemia virus, and feline immunodeficiency virus infections. However, the role of type I IFNs in the pathogenesis of canine diseases remains largely undetermined so far, even though some share pathogenic mechanisms and clinical features with their human counterparts. This review summarizes the present knowledge of type I IFNs and down-stream targets such as Mx and 2',5'-oligoadenylate synthetase proteins in the pathogenesis of infectious and immune-mediated canine diseases. Moreover, studies investigating the potential use of type I IFNs in the treatment of canine lymphomas, melanomas, sarcomas, and carcinomas, canine distemper virus, parvovirus, and papillomavirus infections as well as immune-mediated keratoconjunctivitis sicca and atopic dermatitis are presented. A separate chapter is dedicated to the therapeutic potential of IFN-λ, a type III IFN, in canine diseases. However, further future studies are still needed to unravel the exact functions of the different subtypes of type I IFNs and their target genes in healthy and diseased dogs and the full potential action of type I IFNs as treatment strategy.