Marek's disease virus-induced transient paralysis: clinical and electrophysiologic findings in susceptible and resistant lines of chickens.

Results of neurologic examination, EEG, and motor nerve conduction velocity quantitation were analyzed in a line of chickens susceptible to Marek's disease virus-induced transient paralysis and compared with findings in a resistant line. Both lines were evaluated on the day before virus inoculation (day 1; base line) and on days 12 and 19. The susceptible birds frequently became depressed and paretic on day 11 or 12 and then recovered, and the resistant line rarely was affected clinically. The EEG of clinically affected birds from the susceptible line correlated well with the clinical course of the disease. Electroencephalographic abnormalities were absent in these birds at base line, evident at 12 days, and had remitted when they were reevaluated on day 19. The pattern in these clinically affected birds was predominantly low voltage-fast activity with frequent spikes. In contrast, the EEG recorded in resistant birds remained essentially the same throughout the study. Mean motor nerve conduction velocity values for the 2 lines of birds did not differ significantly when compared either between or within groups. These findings indicate that Marek's disease virus-induced transient paralysis may be an inflammatory encephalopathy.

Motor nerve conduction velocity in normal chickens.

Muscle potentials evoked by proximal and distal tibial nerve stimulation were evaluated and used to calculate motor nerve conduction velocity in 65 chickens. Two potentials analogous to the M and F waves recorded in persons consistently were evoked. The mean tibial motor nerve conduction velocity +/- SD of the birds was 32.3 +/- 4.0 m/s. This value varied significantly (P less than 0.05) with both age and cloacal temperature.

Morphologic alterations associated with decreased cerebrospinal fluid pressure in chronic bovine hypervitaminosis A.

Arachnoid granulations and villi, choroid plexuses, and ependymal epithelium from 18 male Holstein-Friesian calves fed 108 (control), 8,800 (midly toxic), or 17,600 (severely toxic) mug of vitamin A/kg of live weight per day for 12 weeks were examined by light and electron microscopy for structural changes which could be used to explain the decreased cerebrospinal fluid (CSF) pressure seen in chronic hypervitaminotic A animals. In the toxic calf group, granulations were reduced to approximately two-thirds the size of those in the control calves, with the fibrous cap particularly being thinner and smaller. Second, height of epithelial cells of the lateral and 3rd ventricular choroid plexuses decreased significantly and that of the 4th ventricular choroid plexus, only slightly, as vitamin A intake increased. Structural differences of ependymal cells were not apparent between control and hypervitaminotic A calves. It is hypothesized that the thinner and less extensive fibrous cap of the arachnoid granulations in the toxic calves may result in increased permeability to CSF outflow.

Isolation of a herpesvirus from the cell culture of a malignant melanoma of a ground squirrel (Spermophilus tridecemlineatus).

A subcutaneous neoplastic mass in a 13-lined ground squirrel which metastasized to regional lymph nodes and lung was studied. Histopathologically, the tumor architecture and cellular morphology were compatible with that of a malignant amelanotic melanoma. Ultrastructurally, the neoplastic tissue was composed of oval cells, spindle-shaped cells, and spindle-shaped cells with electron-dense cytoplasmic granules. Virus particles were not seen in these cells. Cell cultures from neoplastic tissue grew in complete monolayers and on initial passages contained a few herpesvirus particles. Secondary monolayer cell culture, when exposed to 5-iodo-2'-deoxyuridine or made into several serial subculture passages, caused the appearance of cytopathic effect and the demonstration of many virus particles. The ground squirrel agent, because it contained DNA, was sensitive to chloroform treated and had herpesvirus characteristics on electron microscopy, was considered a herpesvirus. The buoyant density of the virus was 1.298 g/cm3 and the diameter of the enveloped virus particles was 146 nm. This ground squirrel herpesvirus was antigenically distinct from other known herpesviruses.

Polymyositis in dogs.

Polymyositis was diagnosed in nine dogs. Factors utilized in making the diagnosis included (1) muscle pain or weakness, (2) high concentrations of serum muscle enzymes, (3) electromyographic abnormalities, and (4) histopathologic evidence of muscle necrosis and inflammation. Clinical signs included muscle pain, weakness, stilted gait, and pyrexia. Serum muscle enzyme concentrations were high in only three dogs. There was no apparent correlation between enzyme concentrations and severity of clinical involvement or degree of muscle necrosis on biopsy. Electromyographic changes included polyphasic motor unit potentials, fibrillation potentials, and positive waves. Variable degrees of muscle regeneration, degeneration, and inflammation were seen. Prednisone (2.2 mg/kg, OD, per os) was used effectively to treat four dogs. One dog improved initially but was euthanatized later when clinical signs became more pronounced. Three other dogs developed aspiration pneumonia secondary to megaesophagus and either died or were euthanatized.

Marek's disease virus-induced transient paralysis in chickens: electron microscopic lesions.

A study was made to determine the causative lesion of Marek's disease virus (MDV)-induced transient paralysis (TP) in chickens by comparing the ultrastructure of brain tissue from MDV-infected genetically susceptible and resistant birds. There were numerous intramyelinic vacuoles in the brains of TP-affected birds. Many of these vacuoles contained particulate material compatible with precipitated protein from edema. Astrocyte processes often were distended with similar particulate material. Most intramyelinic vacuoles were either adjacent to the axolemma or within inner myelin lamellae. Myelin sheaths of affected axons, while being displaced, were relatively normal with no vesiculation. Most affected axons were also otherwise normal. Cell processes adjacent to occasional affected axons were distended by degenerating mitochondria, vacuoles, and amorphous material. Some of these processes appeared to be inner loops of oligodendrocyte cytoplasm. The cell bodies of most oligodendrocytes were normal, but a few contained vacuoles similar to those seen in processes adjacent to axons. There were scattered necrotic cells. While most of these could not be specifically identified, some appeared to be oligodendrocytes. Mononuclear inflammatory cells were present both perivascularly and within the parenchyma. Although these cells occasionally contacted myelinated axons and there was myelin phagocytosis, there was no indication that they initiated demyelination. Brain tissue from virus-inoculated resistant birds had perivascular aggregates of mononuclear cells, but there were no intramyelinic vacuoles and few necrotic cells. These findings suggest that intramyelinic vacuolation contributes to the pathogenesis of transient paralysis. Potential pathophysiological mechanisms contributing to the vacuoles, including brain edema and oligodendrocyte injury, are discussed.

Intracranial epidermoid cysts in three dogs.

Intracranial epidermoid cysts were identified within the fourth ventricle of three dogs. The cysts measured up to 2.5 cm in diameter, were lined by stratified squamous epithelium, and contained intraluminal keratinaceous debris. Secondary compression of the medulla oblongata and cerebellum caused neurologic dysfunction in two dogs; the cysts was an incidental finding in the other dog. Similarities between these dogs and three previously reported intracranial epidermoid cysts in dogs included an apparent predilection for young dogs and involvement of the cerebellopontine angle, fourth ventricle, or both.

Interspecies transmission of Creutzfeldt-Jakob disease to Syrian hamsters with reference to clinical syndromes and strains of agent.

Experimental Creutzfeldt-Jakob disease was serially transmitted from guinea pigs to Syrian hamsters with 100% incidence, morbidity, and mortality. All animals developed a subacute spongiform virus encephalopathy with neuronal destruction and concomitant astrocytic changes. In the first passage three different clinical syndromes were recorded, each with widely variant incubation times; these results suggested there may be different strains of the Creutzfeldt-Jakob agent, some of which may be partially separated when the agent is passaged from one species to another. Accumulations of neurofilaments in neuronal perikarya and processes and increased lipofuscin were suggestive of changes seen in senility and aging.

Transgenic mice expressing a human poliovirus receptor: a new model for poliomyelitis.

A human poliovirus receptor (PVR) gene was used to generate transgenic mice that express PVR transcripts and poliovirus binding sites in a wide range of tissues. Intracerebral inoculation of PVR transgenic mice with poliovirus type 1, Mahoney strain, resulted in viral replication in the brain and spinal cord and development of paralytic poliomyelitis. P1/Mahoney did not replicate or cause paralysis in nontransgenic mice. PVR transgenic mice failed to develop clinical disease when inoculated intracerebrally with the live attenuated Sabin type 1 vaccine strain. These results demonstrate that the PVR is the major determinant of poliovirus host range in mice. Transgenic mice expressing human PVR should be useful for studying poliovirus neurovirulence, attenuation, and tissue tropism, and for development and testing of poliovirus vaccine strains.

Paralysis in swine due to focal symmetrical poliomalacia: possible selenium toxicosis.

A paralytic disease in swine was observed on three farms located in the same geographical area of Georgia. Postmortem examinations revealed the paralysis to be related to spinal poliomalacia. Feed collected from two of the affected farms was used in a feeding study, and the paralytic condition was reproduced. In pigs from both the feeding trial and field cases, the poliomyelomalacia was characterized by focal, symmetrical lesions located in the cervical and lumbar intumescences. Selenium was detected in the feed at levels ranging from 19 to 24 ppm.

Significance of a newly identified attenuating mutation in Sabin 3 oral poliovirus vaccine.

Sequence analysis of poliovirus vaccine RNA has resulted in the identification of a new point mutation at position 2493 in Sabin 3. cDNA-derived Sabin 3 virus whose genome includes the new mutation has phenotypic properties expected for a vaccine strain. Virus engineered to contain a single base substitution at 2493 has lost the small plaque phenotype, and low neurovirulence characteristics normally associated with Sabin poliovirus strains. The significance of these observations and a potential relationship to the frequency of vaccine-associated poliomyelitis are described.

Marek's disease virus-induced transient paralysis: a comparison of lesions in susceptible and resistant lines of chickens.

A study was conducted to determine the causative lesion of Marek's disease virus-induced transient paralysis. Brain histologic lesions were quantitated and compared in genetically resistant and susceptible inbred chickens. Comparisons were made 11 days post inoculation (PI) of virus when clinical signs were evident in susceptible birds and on day 17 PI when these signs had remitted. Clinically-affected birds from the susceptible line on day 11 PI had consistent evidence of neuropil vacuolation compatible with brain edema; two of these birds also had vasculitis. These lesions were absent in both clinically-recovered birds from this line evaluated on day 17 PI and genetically resistant birds studied on day 11 PI. Our findings suggest that the causative lesion of transient paralysis is vasogenic brain edema.

A mutation present in the amino terminus of Sabin 3 poliovirus VP1 protein is attenuating.

The attenuated phenotype of Sabin 3 poliovirus compared with its neurovirulent progenitor strain has been largely accounted for by mutations in the genome at positions 472 and 2034 (G. D. Westrop, K. A. Wareham, D. M. A. Evans, G. Dunn, P. D. Minor, D. I. Magrath, F. Taffs, S. Marsden, M. A. Skinner, G. C. Schild, and J. W. Almond, J. Virol. 63:1338-1344, 1989). By sequencing vaccine virus RNA, we recently identified another Sabin 3-specific mutation at position 2493 (U----C), which predicts an Ile----Thr change at the sixth residue of VP1 (C. Weeks-Levy, J. M. Tatem, S. J. DiMichele, W. Waterfield, A. F. Georgiu, and S. J. Mento, Virology 185:934-937, 1991). Viruses generated by using cDNAs which represent the vaccine sequence (LED3) and a derivative (VR318) possessing a single base change to the wild-type nucleotide (U) at 2493 were used to determine the impact of the 2493 mutation on virus phenotype. The VP1 proteins of LED3 and VR318 viruses were distinguishable by denaturing electrophoretic analysis. LED3 produced smaller plaques in Vero cells than VR318 virus did. Neurovirulence testing of these cDNA-derived viruses in monkeys demonstrated that the 2493 mutation in LED3 virus is attenuating.