Histopathological Analysis of Brains from Dogs Infected with Canine Distemper Virus.

We describe the use of conventional histology and immunohistochemistry against canine distemper virus (CDV) to examine the brains of domestic dogs with a confirmed diagnosis of CDV infection. Histologically, to identify the main typical lesions, we used conventional H&E stain; to evaluate the progressive demyelination, we used Luxol Fast Blue stain; and to identify the presence of viral particles in these affected regions, we used immunohistochemistry against CDV. We confirm that the histopathological analysis of brains of distemper-infected dogs is a powerful tool to evaluate the typical brain lesions and could be used as an interesting natural model to continue studying the pathogenesis of canine distemper in different species and/or other morbillivirus infections, like measles.

Canine Distemper Virus Pathogenesis in the Ferret Model.

Canine distemper virus (CDV) is a highly contagious pathogen within the morbillivirus genus infecting a wide range of different carnivore species. The virus shares most biological features with other closely related morbilliviruses, including clinical signs, tissue tropism, and replication cycle in the respective host organisms.In the laboratory environment, experimental infections of ferrets with CDV were established as a potent surrogate model for the analysis of several aspects of the biology of the human morbillivirus, measles virus (MeV). The animals are naturally susceptible to CDV and display severe clinical signs resembling the disease seen in patients infected with MeV. As seen with MeV, CDV infects immune cells and is thus associated with a strong transient immunosuppression. Here we describe several methods to evaluate viral load and parameters of immunosuppression in blood-circulating immune cells isolated from CDV-infected animals.

Canine distemper virus infection of vaccinal origin in a 14-week-old puppy.

The body of a 14-wk-old puppy (Canis familiaris) was submitted to the Animal Health Laboratory, University of Guelph, Ontario for postmortem examination following a history of intermittent anorexia and lethargy progressing to pyrexia, pruritic skin rash, mucoid nasal discharge, decreased mentation, dysphagia, muscle twitches, and focal seizures. Gross examination revealed rhinitis and pulmonary edema. Histologically, there was fibrinonecrotizing bronchopneumonia, tracheitis, and neutrophilic and lymphohistiocytic rhinitis; rarely within the cortical gray and white matter of the brain were small clusters of glial cells, with rare individual neutrophils in the choroid plexus. Although canine distemper was suspected, none of the usual supportive histologic lesions of distinct syncytial cells, viral inclusion bodies, or demyelinating leukoencephalitis were observed. Lung and brain tissues were PCR-positive for canine distemper virus (CDV), and CDV was detected immunohistochemically in the brain. The agent from the PCR-positive sample from the brain was genotyped and was a 99.9% match to the CDV Rockborn strain, indicating that the disease agent in our case was vaccinal in origin. Our unusual case highlights the possibility of reversion to virulence in a modified-live virus vaccine, and the occurrence of a disease in the absence of a full complement of the usual and compatible histologic lesions.

Virus discovery in dogs with non-suppurative encephalitis reveals a high incidence of tick-borne encephalitis virus infections in Switzerland.

INTRODUCTION: Viral infections are a frequent cause of disseminated non-suppurative encephalitis in dogs. However, using routine diagnostic methods, the specific virus may remain unknown due to extensive or complete viral clearance or because the virus is unexpected or new. A metatranscriptomics-based approach of combining high-throughput sequencing (HTS) and bioinformatics analysis was used to investigate the viral etiology in archival cases of dogs with non-suppurative encephalitis. In formalin-fixed paraffin embedded (FFPE) brain material from the years 1976 to 2021 a high incidence of tick-borne encephalitis virus (TBEV) was detected. Moreover, canine distemper virus (CDV) was identified without typical demyelinating lesions and canine vesivirus (CaVV) was detected as an unexpected virus associated with non-suppurative encephalitis. We demonstrated the viral presence in brain tissues at the sites of inflammation by immunohistochemistry (IHC) and in situ hybridization (ISH). These results highlight the value of emerging sequencing technologies in veterinary diagnostics and expand our knowledge on the etiologies of encephalitis in dogs.

INTRODUCTION: Les infections virales sont une cause fréquente d'encéphalite non suppurée disséminée chez le chien. Cependant, en utilisant les méthodes de diagnostic de routine, le virus spécifique peut rester inconnu en raison d'une clairance virale importante ou complète ou parce que le virus est inattendu ou nouveau. Une approche métatranscriptomique combinant le séquençage à haut débit et l'analyse bioinformatique a été utilisée pour étudier l'étiologie virale dans des cas archivés de chiens atteints d'encéphalite non suppurée. Une incidence élevée du virus de l'encéphalite à tiques (TBEV) a été détectée dans le matériel cérébral fixé au formol et inclus dans la paraffine (FFPE) des années 1976 à 2021. En outre, le virus de la maladie de Carré (CDV) a été identifié sans lésions démyélinisantes typiques et le vésivirus canin (CaVV) a été détecté comme un virus inattendu associé à une encéphalite non suppurative. Nous avons démontré la présence virale dans les tissus cérébraux au niveau des sites d'inflammation par immunohistochimie (IHC) et hybridation in situ (ISH). Ces résultats soulignent la valeur des technologies de séquençage émergentes dans le diagnostic vétérinaire et élargissent nos connaissances sur les étiologies de l'encéphalite chez les chiens.

Infection of ferrets with wild type-based recombinant canine distemper virus overwhelms the immune system and causes fatal systemic disease.

Canine distemper virus (CDV) causes systemic infection resulting in severe and often fatal disease in a large spectrum of animal host species. The virus is closely related to measles virus and targets myeloid, lymphoid, and epithelial cells, but CDV is more virulent and the infection spreads more rapidly within the infected host. Here, we aimed to study the pathogenesis of wild-type CDV infection by experimentally inoculating ferrets with recombinant CDV (rCDV) based on an isolate directly obtained from a naturally infected raccoon. The recombinant virus was engineered to express a fluorescent reporter protein, facilitating assessment of viral tropism and virulence. In ferrets, this wild type-based rCDV infected myeloid, lymphoid, and epithelial cells, and the infection resulted in systemic dissemination to multiple tissues and organs, especially those of the lymphatic system. High infection percentages in immune cells resulted in depletion of these cells both from circulation and from lymphoid tissues. The majority of CDV-infected ferrets reached their humane endpoints within 20 d and had to be euthanized. In that period, the virus also reached the central nervous system in several ferrets, but we did not observe the development of neurological complications during the study period of 23 d. Two out of 14 ferrets survived CDV infection and developed neutralizing antibodies. We show for the first time the pathogenesis of a non-adapted wild type-based rCDV in ferrets. IMPORTANCE Infection of ferrets with recombinant canine distemper virus (rCDV) expressing a fluorescent reporter protein has been used as proxy to understand measles pathogenesis and immune suppression in humans. CDV and measles virus use the same cellular receptors, but CDV is more virulent, and infection is often associated with neurological complications. rCDV strains in current use have complicated passage histories, which may have affected their pathogenesis. Here, we studied the pathogenesis of the first wild type-based rCDV in ferrets. We used macroscopic fluorescence to identify infected cells and tissues; multicolor flow cytometry to determine viral tropism in immune cells; and histopathology and immunohistochemistry to characterize infected cells and lesions in tissues. We conclude that CDV often overwhelmed the immune system, resulting in viral dissemination to multiple tissues in the absence of a detectable neutralizing antibody response. This virus is a promising tool to study the pathogenesis of morbillivirus infections.

Canine distemper virus and canine adenovirus type 1 co-infection in a free-living hoary fox (Lycalopex vetulus) from Brazil.

The present case is the first description of a co-infection with canine distemper virus (CDV) and canine adenovirus type 1 (CAdV-1) in a free-living hoary fox pup from Brazil. The animal was found and rescued with poor body condition, dehydration, incoordination, ataxia, excessive vocalization, and "blue eyes" phenomenon. Despite the efforts, euthanasia was elected due to worsening clinical signs and poor prognosis. Pathologic examination revealed a mild, acute, random, necrotizing hepatitis, acute bronchopneumonia, hydrocephalus, corneal edema with epithelium degeneration, and acidophilic intracytoplasmatic inclusion bodies in different epithelial cells types with rare syncytial. Through immunohistochemistry, CDV antigen was observed in the tongue, trachea, lungs, liver, spleen, stomach, intestine and urinary bladder. Adenovirus antigen was identified in the nucleus of scattered hepatocytes. Polymerase chain reaction and sequencing demonstrated high similarity with CAdV-1 and wild-type strain of CDV close related to Brazilian viral lineages isolated from domestic dogs. Disease surveillance in wildlife animals is essential to assess possible conservation threats and consider the implementation of mitigation or control measures.

Molecular and pathological screening of canine distemper virus in Asiatic lions, tigers, leopards, snow leopards, clouded leopards, leopard cats, jungle cats, civet cats, fishing cat, and jaguar of different states, India.

The present investigation was conducted to rule out canine distemper (CD) diseases in Indian wild felids (Asiatic lions, tigers, leopards, snow leopards, clouded leopards, leopard cats, jungle cats, civet cats, fishing cat, and jaguar). The collected samples were screened for CD virus (CDV) by histopathology (HP), immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) targeting H gene and N gene. The HP and IHC of suspected samples portrayed that 22 [11 leopards, 6 lions, 3 tigers, 1 snow leopard and 1 civet cat] out of 129 (17.05%) wild felids were positive for CD. The major pathological consequences were observed in spleen, lung, kidney and brain. The syncytia and intranuclear as well as intracytoplasmic eosinophilic inclusion bodies were seen in CDV infected cells. Although the histopathological lesions in spleen were more specific and consistent, however, the severe demyelinated leukoencephalitis (usually expected in CD infected dog) was not observed in the brain of any Indian wild felids. Conversely, the CDV antigen has been portrayed via IHC in pancreatic islets of Langerhans of tiger species for the first time in this study. Moreover, the concurrent CD and babesiosis has also been observed in a lioness without a usual coffee-coloured urine. The N gene and H gene of CDV isolates were amplified, sequenced and subsequently constructed the phylogenetic tree. The phylogenetic analysis of H gene revealed that the CDV isolates from Indian lion formed separate clade with CDV isolates from Indian dog and Indian palm civet cat. Furthermore, two CDV isolates from Indian tigers formed clade with Onderstepoort vaccine strain and CDV isolates from dogs of Uttar Pradesh, USA and UK. Evidently, CDV is circulating in Indian wild felids and causing diseases in them.

Canine distemper virus and canine adenovirus type-2 infections in neotropical otters (Lontra longicaudis) from Southern Brazil.

All descriptions of infectious diseases affecting otters were published in the Northern Hemisphere, with no occurrence identified in neotropical otters (Lontra longicaudis). Consequently, a retrospective histopathological study using archival tissue samples from six free-living neotropical otters was done to investigate the possible occurrence of disease patterns associated with common viral infectious disease agents of the domestic dogs. Immunohistochemical (IHC) assays were designed to identify intralesional tissue antigens of canine distemper virus (CDV), and canine adenovirus-1 (CAdV-1) and canine adenovirus-2 (CAdV-2). The most frequent histopathological patterns diagnosed were interstitial pneumonia (83.33%; 6/5) and hepatocellular vacuolar degeneration (50%; 3/6). IHC identified intralesional intracytoplasmic immunoreactivity to CDV antigens in all otters evaluated, with positive immunolabeling occurring within epithelial cells of the lungs, stomach, kidneys, and liver, and skin. Intracytoplasmic CAdV-2 antigens were identified within epithelial cells of the peribronchial glands in four otters with interstitial pneumonia. These findings resulted in singular and simultaneous infections in these neotropical otters, represented the first report of concomitant infections by CDV and CAdV-2 in free-living neotropical otters from the Southern Hemisphere, and suggested that this mammalian species is susceptible to infections by viral disease agents common to the domestic dogs and may develop similar histopathologic disease patterns.

Central nervous system lesions caused by canine distemper virus in 4 vaccinated dogs.

We examined the cerebellum and cerebrum of 4 vaccinated dogs, 3-60-mo-old, that displayed clinical signs of canine distemper virus (CDV) infection, and died 7-40 d after developing neurologic signs. The main histologic lesions were demyelination, gliosis, meningitis, perivascular lymphocytic cuffing, and inclusion bodies. These lesions were similar in all 4 cases regardless of the time since vaccination, except that meningoencephalitis and gliosis were subacute in 3 dogs and chronic in 1 dog. However, these differences did not appear to be related to their vaccination status. Immunohistologically, a CDV-positive immunoreaction was seen mainly in astrocytes, neurons and their axons, lymphocytes around and in the blood vessels of the pia mater and choroid plexus, ependymal cells of each ventricle, and the cells of the choroid plexus. The histologic and immunohistologic changes were similar in the cerebellum and cerebrum. The genetic characterization of the virus strains in 2 of these naturally occurring canine distemper cases confirmed that they were South American wild-type strains (Kiki and Uy251) belonging to the EU1/SA1 lineage. These strains are not included in the commercial CDV vaccines available in Uruguay.

A Canine Distemper Virus Retrospective Study Conducted from 2011 to 2019 in Central Italy (Latium and Tuscany Regions).

Canine distemper virus (CDV) is a highly lethal contagious viral pathogen mainly found in domestic and wild canids and mustelids. Although, in Italy, circulating strains of Europe 1, Europe wildlife and Arctic type are reported, data relating to Latium and Tuscany regions are limited. In view of this, through passive surveillance, we investigated the presence of CDV and which strains were circulating in these Regions. From March 2017 to October 2019, a group of 122 subjects were tested for CDV using a PCR protocol described in the literature, with 12 detected positive; analyses were carried out on a set of target samples (brain and lung, conjunctival, nasal and rectal swabs, urine or swab from bladder and intracardiac clot) that was defined for the detection of CDV in both live and dead animals. The rectal swab, easily collected also from live animals, represented the most suitable sample for CDV diagnosis, with 9 positive of the 11 (81.82%) tested. In addition, brain and lung of 15 subjects out of 181 susceptible animals collected between 2011 and 2018, during post mortem investigations in routine diagnostic activity, were CDV positive. Molecular analyses of all positive samples, using a 287 bp fragment located within the conserved N terminus of the morbillivirus nucleoprotein gene, detected the circulation of strain CDV599/2016 (KX545421.1) belonging to the "Europe wildlife" lineage, and of strain CDV12254/2015 (KX024709.1), belonging to the Arctic-lineage, thus confirming the co-circulation of the two lineages, as already noted in previous studies.

CANINE DISTEMPER VIRUS IN THE SEA OTTER (ENHYDRA LUTRIS) POPULATION IN WASHINGTON STATE, USA.

Before 2001, all serosurveys for morbilliviruses in sea otters (Enhydra lutris) in California, Washington, and Alaska, US, documented a 0% seroprevalence. The first published serologic detections of morbillivirus in sea otters occurred in 2001-02 in live-captured Washington sea otters, with a documented 80% seroprevalence. We conducted a retrospective study of sea otter cases from 1989 to 2010 compiled at the US Geological Survey, National Wildlife Health Center to identify cases of morbilliviral disease in Washington sea otters and to characterize the disease using immunohistochemistry, reverse transcription (RT)-PCR, genetic sequencing, virus isolation, and serology. We identified six cases of morbilliviral disease and 12 cases of morbilliviral infection in this population of sea otters during 2000-10. Significant histologic findings included inflammation in the white and gray matter of the brain characterized by lymphoplasmacytic perivascular cuffing, neuronal necrosis, and satellitosis in gray matter and by spongiosis, myelin degeneration, spheroids, and gemistocytes in white matter. Intranuclear and intracytoplasmic viral inclusion bodies were found in neurons, Purkinje cells, and glia. Immunohistochemistry for canine distemper virus (CDV) showed positive staining in neurons, glial cells, and cell processes. A pan-morbillivirus RT-PCR with subsequent restriction endonuclease digestion or sequencing identified CDV. Virus isolation was not successful. Two sea otters with morbilliviral encephalitis showed greater antibody titers to CDV than phocine distemper virus. Histologic changes were confined to the central nervous system and resembled neurologic canine distemper in domestic dogs. Cases of sea otters with morbilliviral infection without histologic changes could represent early infections or incompletely cleared sublethal infections. We found that morbillivirus was present in the Washington sea otter population as early as 2000, and we provide a description of the pathology of canine distemper in sea otters.

Canine distemper virus induces downregulation of GABAA,GABAB, and GAT1 expression in brain tissue of dogs.

The aim of the study was to determine the expression profiles of GABAA, GABAB, and GAT1 using RT-PCR and the immunoreactivity of GAT1 via immunohistochemical and immunofluorescence assays in CDV-infected brain tissue of dogs. For this purpose, dogs with CDV and dogs without CDV were selected. The mRNA transcript levels of GABAA, GABAB, and GAT1 were significantly downregulated in brain tissue in the CDV-infected group as compared with that in non-CDV-infected brain tissue in the control group (p < 0.01, p < 0.001). In addition, the immunoreactivity of GAT1 in CDV-infected brain tissue was significantly lower than in the uninfected group (p < 0.05). We conclude that one of the main causes of myoclonus in CDV infections may be the blockage of postsynaptic inhibition in neurons or a lack of metabolism of GABA. In addition, a GABA neurotransmission imbalance could play a role in demyelination in CDV infections.

Natural Canine Distemper Virus Infection in Linnaeus's 2-Toed Sloths (Choloepus didactylus).

An outbreak of canine distemper virus in a private zoo in eastern Tennessee in July 2016 led to fatal clinical disease in 5 adult, wild-caught Linnaeus's 2-toed sloths (Choloepus didactylus). Clinical signs included hyporexia, lethargy, mucopurulent nasal discharge, and oral and facial ulcers. At necropsy, affected animals had crusts and ulcers on the lips, nose, tongue, and oral cavity. Microscopically, all sloths had widespread, random, hepatic necrosis; lymphoid depletion; and bronchointerstitial pneumonia. The central nervous system did not contain gross or histopathologic lesions in any of the 5 sloths, although immunoreactivity for viral antigen was present within vessel walls. Epithelial cells and histiocytes within numerous organs contained intranuclear and intracytoplasmic inclusions and occasional syncytial cells. Canine distemper virus was confirmed with immunohistochemistry and virus isolation. Viral sequencing identified the novel American-4 strain prevalent in eastern Tennessee wildlife. This is the first pathologic characterization of canine distemper virus infection in sloths (family Choloepodidae, order Pilosa) and emphasizes the significant morbidity and mortality in this species.

Immunohistochemical evidence of canine morbillivirus (canine distemper) infection in coatis (Nasua nasua) from Southern Brazil.

The pathological and immunohistochemical (IHC) findings associated with infection due to canine morbilivírus (canine distemper virus, CDV) are described in coatis (Nasua nasua). Tissue fragments of coatis (n = 13) that died at the Bela Vista Sanctuary, Paraná, Southern Brazil, were routinely processed for histopathology to identify the main histopathologic patterns as compared to that of the domestic dog. Selected formalin-fixed paraffin-embedded (FFPE) tissue fragments of the lungs, liver, urinary bladder and small intestine were used in IHC assays designed to identify the antigens of CDV, canine adenovirus (CAdV-1 and CAdV-2) and canine parvovirus type 2 (CPV-2). The main histopathologic patterns identified were interstitial pneumonia (n = 9), interstitial nephritis (n = 6), atrophic enteritis (n = 4) and ballooning degeneration of the uroepithelium (n = 3). Positive immunolabelling for intralesional antigens of CDV was identified in the lung with interstitial pneumonia (n = 3), in the intestine (n = 2) and in the degenerated epithelium of the urinary bladder (n = 2). Antigens of CPV-2, CAdV-1 and CAdV-2 were not identified in any FFPE tissue sections evaluated. These findings indicate that these wild carnivores were infected by a viral disease pathogen common to the domestic dog and develop similar histopathologic findings. Collectively, these findings suggest that these coatis were infected by CDV and can serve as a potential host for this infectious disease pathogen.

Distemper Encephalomyelitis Presenting with Lower Motor Neuron Signs in a Young Dog.

A 4 mo old spayed female mixed-breed dog was presented for focal lower motor neuron signs of the right forelimb and marked hyperesthesia on axillary palpation. Her signs progressed rapidly over the following days to diffuse lower motor neuron signs in all limbs and a seizure. MRI demonstrated a focal, slightly right-sided, 2.5 cm region of noncontrast-enhancing T2 hyperintensity and T1 isointensity at C4-C5 spinal cord segments. Imaging of the brain was unremarkable. The dog was euthanized as a result of poor prognosis. Polymerase chain reaction on cerebrospinal fluid and immunohistochemistry of brain tissue were both positive for canine distemper virus. This report documents an atypical presentation of canine distemper encephalomyelitis causing lower motor neuron signs and hyperesthesia.

Immunohistochemical identification of antigens of canine distemper virus in neotropical felids from Southern Brazil.

The pathologic and immunohistochemical findings associated with infections due to canine distemper virus (CDV) are described in the cougar (Puma concolor), margay (Leopardus wiedii) and jaguarundi (Herpailurus yagouaroundi) from Southern Brazil. Tissue sections of the neotropical felids (n = 3) that died at the Bela Vista Sanctuary, Paraná, Southern Brazil were routinely processed for histopathology to identify possible histopathologic patterns associated with infections due to CDV. Selected formalin-fixed paraffin embedded tissue sections of the lungs and urinary bladder were used in immunohistochemical assays designed to identify the antigens of CDV. The main histopathologic patterns identified were interstitial pneumonia in the margay and jaguarundi, while ballooning degeneration of the transitional epithelium of the urinary bladder was observed in the cougar. Positive immunoreactivity to antigens of CDV was identified within intralesional sections of the lungs of the two wild felids with interstitial pneumonia and in the degenerated urothelium of the cougar. These findings indicate that these neotropical cats were infected by a viral infectious disease pathogen common to the domestic dog and add to the few documented descriptions of CDV-induced infections in wildlife from Brazil.

Detection and Preliminary Characterization of Phocine Distemper Virus in a Stranded Harp Seal (Pagophilus groenlandicus) from the Gulf of St. Lawrence, Canada.

A lethargic juvenile male harp seal (Pagophilus groenlandicus) in poor nutritional condition was found on the beach on the north shore of Prince Edward Island, Canada, in June 2017. Microscopic examination revealed a severe nonsuppurative encephalitis positive for morbillivirus antigen on immunohistochemistry. Virus isolation attempts were negative. However, phocine distemper virus (PDV) was detected in brain tissue RNA extracts by a seminested reverse transcription PCR that targeted the paramyxovirus RNA-dependent RNA polymerase (pol) gene. Comparison of the resulting partial PDV pol nucleotide sequence revealed it was nearly identical to PDV strains isolated from eastern Atlantic harbor seals (Phoca vitulina vitulina) during a 1988 epizootic in the Wadden and Irish seas, and a western Atlantic harbor seal (Phoca vitulina concolor) that stranded in Maine, US, in 2006. Our study confirmed that closely related PDV strains are circulating in multiple seal species along the coastlines of North America and Europe.

Neurotoxic potential of reactive astrocytes in canine distemper demyelinating leukoencephalitis.

Canine distemper virus (CDV) causes a fatal demyelinating leukoencephalitis in young dogs resembling human multiple sclerosis. Astrocytes are the main cellular target of CDV and undergo reactive changes already in pre-demyelinating brain lesions. Based on their broad range of beneficial and detrimental effects in the injured brain reactive astrogliosis is in need of intensive investigation. The aim of the study was to characterize astrocyte plasticity during the course of CDV-induced demyelinating leukoencephalitis by the aid of immunohistochemistry, immunofluorescence and gene expression analysis. Immunohistochemistry revealed the presence of reactive glial fibrillary acidic protein (GFAP)+ astrocytes with increased survivin and reduced aquaporin 4, and glutamine synthetase protein levels, indicating disturbed blood brain barrier function, glutamate homeostasis and astrocyte maladaptation, respectively. Gene expression analysis revealed 81 differentially expressed astrocyte-related genes with a dominance of genes associated with neurotoxic A1-polarized astrocytes. Accordingly, acyl-coA synthetase long-chain family member 5+/GFAP+, and serglycin+/GFAP+ cells, characteristic of A1-astrocytes, were found in demyelinating lesions by immunofluorescence. In addition, gene expression revealed a dysregulation of astrocytic function including disturbed glutamate homeostasis and altered immune function. Observed findings indicate an astrocyte polarization towards a neurotoxic phenotype likely contributing to lesion initiation and progression in canine distemper leukoencephalitis.

Reactive Oxygen Species Are Key Mediators of Demyelination in Canine Distemper Leukoencephalitis but not in Theiler's Murine Encephalomyelitis.

(1) Background: Canine distemper virus (CDV)-induced demyelinating leukoencephalitis (CDV-DL) in dogs and Theiler's murine encephalomyelitis (TME) virus (TMEV)-induced demyelinating leukomyelitis (TMEV-DL) are virus-induced demyelinating conditions mimicking Multiple Sclerosis (MS). Reactive oxygen species (ROS) can induce the degradation of lipids and nucleic acids to characteristic metabolites such as oxidized lipids, malondialdehyde, and 8-hydroxyguanosine. The hypothesis of this study is that ROS are key effector molecules in the pathogenesis of myelin membrane breakdown in CDV-DL and TMEV-DL. (2) Methods: ROS metabolites and antioxidative enzymes were assessed using immunofluorescence in cerebellar lesions of naturally CDV-infected dogs and spinal cord tissue of TMEV-infected mice. The transcription of selected genes involved in ROS generation and detoxification was analyzed using gene-expression microarrays in CDV-DL and TMEV-DL. (3) Results: Immunofluorescence revealed increased amounts of oxidized lipids, malondialdehyde, and 8-hydroxyguanosine in CDV-DL while TMEV-infected mice did not reveal marked changes. In contrast, microarray-analysis showed an upregulated gene expression associated with ROS generation in both diseases. (4) Conclusion: In summary, the present study demonstrates a similar upregulation of gene-expression of ROS generation in CDV-DL and TMEV-DL. However, immunofluorescence revealed increased accumulation of ROS metabolites exclusively in CDV-DL. These results suggest differences in the pathogenesis of demyelination in these two animal models.

New world origin of canine distemper: Interdisciplinary insights.

OBJECTIVE: Canine distemper virus (CDV), human measles virus (HMV), and rinderpest virus (RPV) of cattle are morbilliviruses that have caused devastating outbreaks for centuries. This paper seeks to reconstruct the evolutionary history of CDV. MATERIALS AND METHODS: An interdisciplinary approach is adopted, synthesizing paleopathological analysis of 96 Pre-Columbian dogs (750-1470 CE) from the Weyanoke Old Town, Virginia site, with historical reports, molecular analysis and morbilliviral epidemiology. RESULTS: Both measles (c.900CE) and rinderpest (c. 376 BCE) were first reported in Eurasia, while canine distemper was initially described in South America much later (1735 CE); there are no paleopathological indications of CDV in Weyanoke Old Town dogs. Molecularly, CDV is closely related to HMV, while viral codon usage indicates CDV may have previously infected humans; South American measles epidemics occurred prior to the emergence of canine distemper and would have facilitated HMV transmission and adaptation to dogs. CONCLUSIONS: The measles epidemics that decimated indigenous South American populations in the 1500-1700 s likely facilitated the establishment of CDV as a canine pathogen, which eventually spread to Europe and beyond. SIGNIFICANCE: Understanding the historical and environmental conditions that have driven morbilliviral evolution provides important insights into potential future threats of animal/human cross-species infections. LIMITATIONS: Interpreting historical disease descriptions is difficult and the archaeological specimens are limited. Molecular sequence data and codon usage analyses rely on modern viruses. SUGGESTIONS FOR FURTHER RESEARCH: Interdisciplinary approaches are increasingly needed to understand diseases of the past and present, as critical information and knowledge is scattered in different disciplines.