Novel feline viruses: Emerging significance of gammaherpesvirus and morbillivirus infections.

PRACTICAL RELEVANCE: New technologies capable of sequencing the genetic material in any given biological sample, combined with computer-based algorithms for sequence assembly and analysis, have revolutionised infectious disease research. The rate at which novel viruses are being discovered now exceeds our understanding of their clinical relevance. Novel viruses may contribute to diseases that are major causes of feline morbidity and mortality, including cancer and chronic kidney disease. The identification of new viral pathogens raises the prospect of not only improved patient outcomes through specific treatment but even disease prevention through viral control measures. CLINICAL CHALLENGES: It can be difficult to determine the role of a novel virus in disease development. Disease may be an occasional outcome, often years after infection. A high prevalence of infection in the general population can make disease associations harder to identify and almost impossible to rule out. Host cofactors such as immune dysfunction, genetic background or coinfections may be required for manifestation of disease, and one virus species may be linked to a range of pathological sequelae. Establishing causality relies on evaluating accumulating evidence from multiple investigations, which is often hard to access by practitioners. GLOBAL IMPORTANCE: The worldwide distribution of gammaherpesvirus and morbillivirus infections in domestic cats underlines the potential of these viruses to negatively impact feline health and welfare globally. EVIDENCE BASE: This review relies on grade la-III evidence.

Detection and seroprevalence of morbillivirus and other paramyxoviruses in geriatric cats with and without evidence of azotemic chronic kidney disease.

BACKGROUND: Feline morbillivirus (FeMV) is associated with the presence of tubulo-interstitial nephritis (TIN) in cats, however the seroprevalence of FeMV in the UK and the association between the presence of FeMV and renal azotemia is unknown HYPOTHESIS/OBJECTIVES: To identify whether paramyxoviruses are present in urine samples of geriatric cats and to develop an assay to assess FeMV seroprevalence. To investigate the relationship between both urinary paramyxovirus (including FeMV) excretion and FeMV seroprevalence and azotemic chronic kidney disease (CKD). ANIMALS: Seventy-nine cats (40 for FeMV detection; 72 for seroprevalence). METHODS: Retrospective cross-sectional, case control study. Viral RNA was extracted from urine for RT-PCR. PCR products were sequenced for virus identification and comparison. The FeMV N protein gene was cloned and partially purified for use as an antigen to screen cat sera for anti-FeMV antibodies by Western Blot. RESULTS: Feline morbillivirus RNA from five distinct morbilliviruses were identified. Detection was not significantly different between azotemic CKD (1/16) and nonazotemic groups (4/24; P = .36). Three distinct, non-FeMV paramyxoviruses were present in the nonazotemic group but their absence from the azotemic group was not statistically significant (P = .15). 6/14 (43%) azotemic cats and 40/55 (73%) nonazotemic cats were seropositive (P = .06). CONCLUSIONS AND CLINICAL IMPORTANCE: Feline morbillivirus was detected in cats in the UK for the First time. However, there was no association between virus prevalence or seropositivity and azotemic CKD. These data do not support the hypothesis that FeMV infection is associated with the development of azotemic CKD in cats in the UK.

Coinfection by Streptococcus phocae and cetacean morbillivirus in a short-beaked common dolphin Delphinus delphis.

We describe gross, histopathological, and immunohistochemical features of Streptococcus phocae and cetacean morbillivirus coinfection in a short-beaked common dolphin Delphinus delphis. Major gross findings were cutaneous purulent nodules in the tail fluke, vegetative mitral valve endocarditis, and presumed postpartum pyometra. Histologic examination revealed bacterial septicemia characterized by widespread intravascular coccoid bacterial emboli. These were associated with fibrinonecrotizing to pyogranulomatous dermatitis and panniculitis, embolic pneumonia, neutrophilic and lymphoplasmacytic meningochoroiditis, random neutrophilic hepatitis, lymphoplasmacytic myocarditis and epicarditis, necrotizing adrenalitis, suppurative endometritis, and multicentric reactive lymphadenopathy. Bacteriology and molecular analysis with sequencing of the 16S rRNA gene identified S. phocae from lung, brain, and adrenal gland tissue. Immunohistochemical analysis for morbillivirus detection revealed positive immunolabeling in the epithelium of the choroid plexus of the fourth ventricle. Published reports on S. phocae infection in cetaceans are rare, and pathological details are limited. The present case indicates that S. phocae has potential pathogenic capacity in common dolphins. The pathogenesis is proposed to have involved cutaneous penetration after a skin trauma, leading to initial cutaneous disease and eventual systemic infection.

Dolphin Morbillivirus and Toxoplasma gondii coinfection in a Mediterranean fin whale (Balaenoptera physalus).

BACKGROUND: Although Morbillivirus and Toxoplasma gondii have emerged as important pathogens for several cetaceans populations over the last 20 years, they have never been identified together in a Mysticete. In particular, morbilliviral infection has been never described in the Mediterranean fin whale population. CASE PRESENTATION: On January 2011 an adult male of fin whale (Balaenoptera physalus) stranded along the Tyrrhenian coastline of Italy. During necropsy, tissue samples from heart, skeletal muscle, mesenteric lymph nodes, liver, spleen, lung, and kidney were collected and subsequently analyzed for Morbillivirus and Toxoplasma gondii by microscopic and molecular methods. Following the detailed necropsy carried out on this whale, molecular analysis revealed, for the first time, the simultaneous presence of a Dolphin Morbillivirus (DMV) and T. gondii infection coexisting with each other, along with high organochlorine pollutant concentrations, with special reference to DDT. CONCLUSION: This report, besides confirming the possibility for Mysticetes to be infected with DMV, highlights the risk of toxoplasmosis in sea water for mammals, already immunodepressed by concurrent factors as infections and environmental contaminants.

Systemic herpesvirus and morbillivirus co-infection in a striped dolphin (Stenella coeruleoalba).

During 2007 a dolphin morbillivirus epizootic affected the western Mediterranean and several striped dolphins (Stenella coeruleoalba) stranded on the Catalonian coasts. One of those animals had severe lymphoid depletion, necrosis and syncytial formation in lymph nodes and spleen, with large basophilic nuclear inclusions compatible with herpesvirus detected by immunohistochemical and ultrastructural examination. Non-suppurative encephalitis with associated morbillivirus antigen and morbillivirus antigen within alveolar macrophages were also observed. A pan-herpesvirus nested polymerase chain reaction amplified a sequence virtually identical to two cetacean herpesvirus sequences previously identified in systemic infections in an Atlantic Cuvier's beaked whale (Ziphius cavirostris) and in a Mediterranean striped dolphin. The herpesviral infection was probably secondary to the immunosuppression caused by the morbillivirus. To our knowledge, this is the first report of a cetacean co-infected by dolphin morbillivirus and herpesvirus with evidence of lesions attributable to both viruses.

Presence of herpesvirus in striped dolphins stranded during the cetacean morbillivirus epizootic along the Mediterranean Spanish coast in 2007.

A screening for herpesvirus (HV) was carried out using a tissue bank obtained from the cetacean morbillivirus (CeMV) mortality episode that occurred along the Mediterranean Spanish coast in 2007. A total of 14 cetaceans, including six long-finned pilot whales and eight striped dolphins, were studied using histopathology and molecular analysis to detect HV and CeMV. In five of the eight dolphins (62.5%) infected with CeMV, eight novel HV sequences were also detected. No HV lesions were found in any of the coinfected dolphins, which may indicate that HV did not contribute to the mortality in the CeMV outbreak. This is the first report of HV infection in any cetacean from the Mediterranean Sea.

Ferrets as a model for morbillivirus pathogenesis, complications, and vaccines.

The ferret is a standard laboratory animal that can be accommodated in most animal facilities. While not susceptible to measles, ferrets are a natural host of canine distemper virus (CDV), the closely related carnivore morbillivirus. CDV infection in ferrets reproduces all clinical signs associated with measles in humans, including the typical rash, fever, general immunosuppression, gastrointestinal and respiratory involvement, and neurological complications. Due to this similarity, experimental CDV infection of ferrets is frequently used to assess the efficacy of novel vaccines, and to characterize pathogenesis mechanisms. In addition, direct intracranial inoculation of measles isolates from subacute sclerosing panencephalitis (SSPE) patients results in an SSPE-like disease in animals that survive the acute phase. Since the advent of reverse genetics systems that allow the targeted manipulation of viral genomes, the model has been used to evaluate the contribution of the accessory proteins C and V, and signalling lymphocyte activation molecule (SLAM)-binding to immunosuppression and overall pathogenesis. Similarly produced green fluorescent protein-expressing derivatives that maintain parental virulence have been instrumental in the direct visualization of systemic dissemination and neuroinvasion. As more immunological tools become available for this model, its contribution to our understanding of morbillivirus-host interactions is expected to increase.

Changes in epizoic crustacean infestations during cetacean die-offs: the mass mortality of Mediterranean striped dolphins Stenella coeruleoalba revisited.

In the summer and autumn of 1990, a cetacean morbillivirus caused a massive epizootic mortality of striped dolphins Stenella coeruleoalba in the western Mediterranean. Previous circumstantial evidence suggested that the disease could also have increased host susceptibility to infestations with epizoic crustaceans. In this study we provide strong evidence supporting this hypothesis. We examined striped dolphins stranded along the Mediterranean central coast of Spain from 1981 to 2004 (n = 136), and recorded data on prevalence, intensity of infestation, size and reproductive status of 2 sessile crustacean species specific to cetaceans, the phoront cirriped Xenobalanus globicipitis and the mesoparasitic copepod Pennella balaenopterae. Compared with the pre-epizootic (n = 12) and post-epizootic (n = 62) dolphin samples, the following changes were noted in the dolphins stranded during the epizootic (n = 62): (1) the prevalence of both X. globicipitis and P. balaenopterae increased; (2) the intensity of X. globicipitis and P. balaenopterae infestations did not increase; indeed, it was even slightly lower than in the other periods, as was their degree of aggregation; (3) individuals of both species were smaller, and a higher proportion were non-gravid; (4) the 2 species tended to co-occur in the same dolphins, but their numbers did not co-vary. These patterns strongly suggest that, during the epizootic, there was a short-term increase in the probability of infestation of these 2 species because of the sudden rise in the population of susceptible hosts; the growth of the new recruits was limited by the early death of dolphins. The high susceptibility was likely related to the immunosuppressive effects of viral infection and the abnormally heavy loads of polychlorinated biphenyls found in sick dolphins; the level of inbreeding was also higher in dolphins from the 'epizootic' sample. Epizoic crustaceans could be suitable indicators of health in cetacean populations.

[Current aspects of the pathogenesis and clinical characteristics of otosclerosis: possibilities of drug therapy]. / Az otosclerosis patogenezisének és klinikumának modern szemlélete: a gyógyszeres terápia lehetöségei.

Otosclerosis is a multifactorial disease. A number of theories on the pathogenesis of this disease have been established in the last decades. It is important to review recent data on the pathogenesis of otosclerosis as it is a severe inner ear disease leading to deafness in the majority of cases. Surgical therapy is not always successful or feasible. In this review, authors describe the most relevant genetic, infective, immunological, inflammatory factors, as well as the impaired bone metabolism underlying the pathogenesis of otosclerosis. It is likely that genetic predisposition associated with morbilli infection may lead to bone resorption in the stapes and cochlea followed by spongiosis, fibrosis and sclerosis. It has been suggested that immunological mechanisms play a central role in the development of the disease. Some authors consider otosclerosis as autoimmune disorder based on the presence of several autoantibodies. Apart from classical diagnostic methods, such as audiometry and X-ray, novel radiological techniques including CT, MRI or radionuclide scan are helpful in the localization of otosclerosis. As surgery is sometimes contraindicated or unsuccessful, drug therapy including the use of anti-osteoporotic on non-steroidal antiinflammatory drugs may be administered, especially in the early phase of the disease.

Dermatitis with invasive ciliated protozoa in dolphins that died during the 1987-1988 Atlantic Bottlenose Dolphin morbilliviral epizootic.

Dermatitis with intradermal cilated protozoa was identified in 18 of 95 (19%) Atlantic Bottlenose Dolphins (Tursiops truncatus) that died during the 1987-1988 Atlantic-dolphin morbillivirus epizootic. The lesions were characterized by focally extensive suppurative and histiocytic dermatitis and cellulitis with ulceration and variable numbers of dermal and hypodermal ciliates. Vasculitis, thrombosis, and/or intravascular ciliates were rarely present. In one dolphin, there was an associated lymphadenitis with ciliates, and in another, bronchopneumonia with rare intrabronchiolar ciliates. Ten of the dolphins were female, and eight were male. The animals ranged in length from 148 to 260 cm. Eleven were from Virginia, four were from New Jersey, and three were from Florida. In 13 dolphins, results of immunohistochemical and/or polymerase chain reaction (PCR) tests were positive for morbillivirus infection. Results of immunohistochemical tests were negative in four dolphins that were not also tested with PCR. Results were also negative in one dolphin tested using both methods. Nine dolphins had concomitant bacterial, fungal, and/or other protozoal infections. Fourteen other dolphins with ciliate-associated dermatitis were identified from 414 Atlantic bottlenose dolphin cases (3%) archived at the Armed Forces Institute of Pathology. The incidence of dermatitis with invasive ciliates is much greater in dolphins that died during the 1987-1988 epizootic.

Luteinized ovarian cysts in Mediterranean striped dolphins.

The morbillivirus epizootic during 1990 to 1992 in Mediterranean striped dolphins (Stenella coeruleoalba) off the Mediterranean coast of Spain diminished these populations directly through mortalities, and indirectly through loss of normal fecundity. High levels of polychlorinated biphenyls (PCB's) also were detected in stranded animals. In addition to high numbers of abortions during the epidemic, unusual cystic structures were noted in the ovaries of several morbillivirus-infected dolphins with high PCB levels. These structures were identified as multiple luteinized cysts from their gross and histomorphologic characteristics. No morbillivirus antigens were detected in the lesions by immunohistochemistry. Because luteinized cysts occur when ovulation is impeded, either an effect of morbillivirus or PCB's on hypothalamic/pituitary function or an effect of PCB's on ovarian responsiveness are proposed as pathogenic mechanisms. These cysts may impede population recovery from the epidemic if similar cysts occurred on surviving dolphins.

Morbilliviral disease in an Atlantic bottlenose dolphin (Tursiops truncatus) from the Gulf of Mexico.

A free-living adult female Atlantic bottlenose dolphin (Tursiops truncatus) found dead near Panama City, Florida (USA), had necrotizing and ulcerative tracheitis, suppurative and hemorrhagic pneumonia, and necrotizing myocarditis; fungal hyphae were present in these lesions. Additionally, lungs had multifocal proliferative interstitial pneumonia with occasional syncytial cells. Some syncytial cells and type II pneumocytes contained eosinophilic intranuclear or intracytoplasmic inclusion bodies, or both. Based on an immunoperoxidase technique, there was morbilliviral antigen within cytoplasm and nuclei of type II pneumocytes and syncytial cells: antigen also occurred in trachea, skin, liver, stomach, intestine, and uterus. Based on pathologic and immunocytochemical findings, the dolphin had morbillivirus-induced disease. This is the first report of morbilliviral disease in a marine mammal from the Gulf of Mexico.

The pathogenesis of Crohn's disease.

This paper describes a program of research undertaken by the Inflammatory Bowel Disease Study Group at the Royal Free Hospital School of Medicine. The Group has tested the hypothesis that the primary pathological abnormality in Crohn's disease is in the mesenteric blood supply. The first experiments involved microcorrosion resin casting of the arterial supply of specimens of resected intestine affected by Crohn's disease. This revealed severe damage to submucosal blood vessels, even in areas that were not affected macroscopically by Crohn's disease. Resected specimens of bowel were examined after perfusion-fixation: 85% of granulomas were associated with blood vessels, demonstrating that Crohn's disease is a granulomatous vasculitis. Patients with Crohn's disease usually have one or more features of a hypercoagulable state, which may increase the risk of ischemic damage. A model of Crohn's disease was developed in the ferret intestine, by embolizing mesenteric blood vessels using latex particles. Acute embolization results in patchy necrosis of the mucosa, with subsequent recovery. Surgical incision and anastomosis in a previously embolized area results in intense ulceration--suggesting that recurrent Crohn's disease after surgery is due to a second ischemic insult to an already damaged intestine. Finally, electron microscope studies have investigated the mesenteric vascular endothelium associated with granulomata in Crohn's disease. Viral particles have been identified within the vascular endothelium, with the appearance of paramyxoviridae. In situ hybridization and other studies suggest that these particles are measles virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Peste des petits ruminants in Ethiopian goats.

An outbreak of disease characterised by fever, ocular and nasal discharge, coughing and sneezing, oral necrosis, diarrhoea, enteritis and pneumonia in goats was shown by the use of specific cDNA probes to have been peste des petits ruminants, confirmed for the first time in Ethiopia. Both morbidity and mortality rates were high in goats but sheep were not affected.

Intestinal lesions in experimental phocine distemper: light microscopy, immunohistochemistry and electron microscopy.

The involvement of the intestinal mucosa and of the gut-associated lymphoid tissue in phocine distemper was studied in six severely diseased harbour seals 11 to 16 days after experimental infection. Five seals exhibited a mild or moderate enteritis in the small or large intestine. In all the seals, a moderate to severe depletion of submucosal lymphoid follicles was found. Likewise, antigen of phocine distemper virus (PDV) was demonstrated immunohistochemically in the intestinal wall of all the seals. Most antigen was found in the submucosal lymphoid follicles, followed by the crypt epithelium and follicle-associated epithelium (FAE). Ultrastructurally, intracytoplasmic tubular structures were detected in the FAE and interpreted as morbilliviral nucleocapsids. The results indicate a direct cytopathogenic effect of PDV on intestinal lymphoid and epithelial cells and suggest an important role of the intestinal tract in phocine distemper and, by analogy, in other morbillivirus infections as a regular site of virus replication, virus shedding and immunosuppression.