A novel enterovirus in lambs with poliomyelitis and brain stem encephalitis.

An Austrian organic dairy sheep farm experienced cases of recumbency and sudden deaths in 3- to 4-week-old lambs. Two animals were subjected to thorough clinical and pathological investigations. Pathohistological analysis identified severe nonsuppurative myelitis and mild nonsuppurative encephalitis. A reverse-transcription quantitative PCR (RT-qPCR) assay for the recently discovered ovine picornavirus causing comparable lesions scored negative. By next-generation sequencing-based metagenomics, a nearly complete genome of a novel enterovirus could be detected and assembled. In situ hybridization using a specifically designed probe revealed robust signals in affected motoneurons of the spinal cord suggesting a causative role of the novel virus.

Astrovirus-Associated Polioencephalomyelitis in an Alpaca.

An 8-year-old alpaca was admitted to the emergency service of the Clinic for Ruminants in Bern due to a reduced general condition and progressive neurological signs. Despite supportive treatment, its condition deteriorated and the animal had to be euthanized. Histopathological analysis revealed a severe non-suppurative polioencephalomyelitis with neuronal necrosis, most likely of viral origin. We detected abundant neuronal labelling with antibodies directed against two different epitopes of Bovine Astrovirus CH13/NeuroS1 (BoAstV-CH13/NeuroS1), which is a common viral agent associated with non-suppurative encephalitis in Swiss cattle. These findings were further verified by detection of viral RNA by use of in-situ hybridization and real-time RT-PCR. Next generation sequencing revealed that the detected virus genome had a pairwise identity of 98.9% to the genome of BoAstV-CH13/NeuroS1. To our knowledge, this is the first report of an astrovirus-associated polioencephalomyelitis in an alpaca. These results point to the possibility of an interspecies transmission of BoAstV-CH13/NeuroS1.

Upregulation of voltage-gated Ca2+ channels in mouse astrocytes infected with Theiler's murine encephalomyelitis virus (TMEV).

Theiler's murine encephalomyelitis virus (TMEV) induces demyelination in susceptible strains of mice through a CD4(+) Th1 T cell-mediated immunopathological process. TMEV infection produces a syndrome in mice that resembles multiple sclerosis. In this work, we focused on the increased expression of the genes encoding voltage-gated Ca(2+) channel subunits in SJL/J mouse astrocytes infected in culture with a BeAn strain of TMEV. Affymetrix DNA murine genome U74v2 DNA microarray hybridized with cRNA from mock- and TMEV-infected astrocytes revealed the upregulation of four sequences encoding Ca(2+)-binding and Ca(2+) channel subunit proteins. The DNA hybridization results were further validated using conventional RT-PCR and quantitative RT-PCR, demonstrating the increased expression of mRNA encoding channel subunit proteins. Western blotting also showed the increased synthesis of L- and N-type channel subunit specific proteins after infection. The reduced expression and the functional upregulation of functional voltage-gated Ca(2+) channels in mock- and TMEV-infected cells, respectively, was demonstrated using voltage clamp experiments. TMEV infection in mouse astrocytes induced a Ca(2+) current with a density proportional to the amount of viral particles used for infection. The use of Ca(2+) channel blockers, nimodipine and ω-conotoxin-GVIA, showed that both functional L- and N-type Ca(2+) channels were upregulated in infected astrocytes. The upregulation of Ca(2+) channels in astrocytes after TMEV infection provides insight into the molecular processes and potential role of astrocyte Ca(2+) dysregulation in the pathophysiology of encephalomyelitis and is important for the development of novel therapeutic strategies leading to prevention of neurodegeneration.

Poliomyelitis in MuLV-infected ICR-SCID mice after injection of basement membrane matrix contaminated with lactate dehydrogenase-elevating virus.

The arterivirus lactate dehydrogenase-elevating virus (LDV) causes life-long viremia in mice. Although LDV infection generally does not cause disease, infected mice that are homozygous for the Fv1(n) allele are prone to develop poliomyelitis when immunosuppressed, a condition known as age-dependent poliomyelitis. The development of age-dependent poliomyelitis requires coinfection with endogenous murine leukemia virus. Even though LDV is a common contaminant of transplantable tumors, clinical signs of poliomyelitis after inadvertent exposure to LDV have not been described in recent literature. In addition, LDV-induced poliomyelitis has not been reported in SCID or ICR mice. Here we describe the occurrence of poliomyelitis in ICR-SCID mice resulting from injection of LDV-contaminated basement membrane matrix. After exposure to LDV, a subset of mice presented with clinical signs including paresis, which was associated with atrophy of the hindlimb musculature, and tachypnea; in addition, some mice died suddenly with or without premonitory signs. Mice presenting within the first 6 mo after infection had regions of spongiosis, neuronal necrosis and astrocytosis of the ventral spinal cord, and less commonly, brainstem. Axonal degeneration of ventral roots prevailed in more chronically infected mice. LDV was identified by RT-PCR in 12 of 15 mice with typical neuropathology; positive antiLDV immunolabeling was identified in all PCR-positive animals (n = 7) tested. Three of 8 mice with neuropathology but no clinical signs were LDV negative by RT-PCR. RT-PCR yielded murine leukemia virus in spinal cords of all mice tested, regardless of clinical presentation or neuropathology.

Evaluation of poliovirus antibody titers in orally vaccinated semi-captive chimpanzees in Uganda.

BACKGROUND: To understand immunological responses in chimpanzees vaccinated with live-attenuated vaccine (oral polio vaccine; OPV), serum neutralizing antibodies against poliovirus types 1, 2, and 3 were investigated over time. METHODS: The neutralizing antibody titers against poliovirus types 1, 2, and 3 were determined by microneutralization test using 100 ID(50) of poliovirus types 1, 2, and 3 (Sabin strains). RESULTS: Neutralizing antibodies against poliovirus types 1, 2, and 3 were detected in 85.7%, 71.4%, and 65% of the serum from 42 chimpanzees tested 9 years post-vaccination. The neutralizing antibody titers in chimpanzees were similar to the documented levels in human studies as an indicator of vaccine efficacy. CONCLUSIONS: This study reveals persistence of neutralizing antibodies in chimpanzees for at least 9 years after vaccination with OPV. This first study in chimpanzees provides useful information for the evaluation of the success of vaccination with OPV in other captive apes.

West Nile Flavivirus Polioencephalomyelitis in a harbor seal (Phoca vitulina).

A 12-year-old male harbor seal presented with progressive signs of neurologic dysfunction including head tremors, muzzle twitching, clonic spasms, and weakness. Lesions included polioencephalomyelitis with glial nodules, spheroids, neuronophagia, ring hemorrhages, and a few neutrophils. Neurons, fibers, and glial nodules were multifocally colonized with intracytoplasmic West Nile flavivirus antigens that were demonstrated using indirect immunohistochemical analysis. Flavivirus on cultured cells also was isolated and was identified by use of monoclonal antibodies and reverse transcriptase-polymerase chain reaction analysis. Clinical signs of disease and lesion morphology and distribution were similar to those of equine West Nile virus infection. Similar to horses, alpacas, humans, dogs, and reptiles, seals can be dead-end hosts of West Nile virus.

Theiler's murine encephalomyelitis virus (TMEV): the role of a small out-of-frame protein in viral persistence and demyelination.

Theiler's murine encephalomyelitis virus (TMEV) belongs to the genus Cardiovirus of the family Picornaviridae and is divided into two subgroups on the basis of different biological activities. GDVII subgroup strains produce acute and fatal polioencephalomyelitis in mice with no virus persistence. In contrast, DA or TO subgroup strains cause an early nonfatal polioencephalomyelitis. TMEV is thought to be an excellent animal model for the human demyelinating disease, multiple sclerosis. Data suggest that macrophages are a major reservoir harboring the virus. A small out-of-frame protein designated L* is synthesized in DA subgroup strains from an alternative, out-of-frame, initiation site. Studies of a DA mutant virus, having an ACG rather than an AUG and therefore does not synthesize L* protein, demonstrate that this protein is important for virus growth in particular cell types and is critical for DA-induced demyelinating disease and virus persistence. In addition, TMEV can be used as a vector for delivering foreign sequences into the central nervous system.

A serological indication of the existence of a guineapig poliovirus.

Attempts were made to clarify whether laboratory guineapigs may harbour a poliovirus which, in 1911, was described as the cause of a disease called guineapig lameness. By the use of ELISA for antibodies against the poliovirus, Theiler's murine encephalomyelitis virus (TMEV), it was shown that two pet shop guineapigs suffering from lameness had extremely high titres against poliovirus, while healthy guineapigs from the same pet shop were negative. Clearly positive results were also found in 35 out of 152 laboratory guineapig sera. Positive results were found in only two out of six breeding centres, but in three out of three experimental units, all of which purchased guineapigs from one of the seropositive breeding colonies. The diseased guineapigs recovered fully after treatment with vitamins in the drinking water, a treatment used for guineapig lameness by small animal practitioners. A theory that vitamin C deficient guineapigs are, due to an impaired steroid secretion, predisposed to succumbing to infection and develop demyelinating disease similar to that in TMEV infected mice is discussed briefly. Guineapig sera were also tested serologically for other infections. Antibodies against lymphocytic choriomeningitis virus, Clostridium piliforme and Toxoplasma gondii were not found, but one breeding colony was infected with adenovirus, pneumonia virus of mice, reovirus type 3, Sendai virus, parainfluenza (simian) virus type 5 and Encephalitozoon cuniculi. Two other breeding colonies were infected with both reovirus type 3 and E. cuniculi. In all three experimental units infection with adenovirus was observed, and in two of these Sendai virus and E. cuniculi antibodies were also found. The pet shop guineapigs were infected with adenovirus, reovirus type 3 and E. cuniculi.

Multiple neurologic deficits. Inflammatory diseases.

Certain diseases do not consistently affect a single area of the nervous system and, in fact, may cause concomitant multifocal involvement. Depending on the area of the nervous system affected, these diseases may cause a wide spectrum of neurologic problems and therefore must be included in the differential diagnosis for most problems discussed previously. Diseases causing multifocal lesions should especially be suspected when there are concomitant neurologic deficits that cannot be localized to a single site. An example would be a cat with seizures and paraparesis without thoracic limb involvement, in which case separate lesions affecting the forebrain and thoracolumbar spinal cord would be suspected. Inflammatory neurologic diseases most commonly cause lesions at multiple sites and will be discussed here. These conditions frequently cause concomitant systemic disease. Additional disease categories that may cause multifocal lesions, and are somewhat more likely to result in strict neurologic disease, are discussed in Multiple Neurologic Deficits: Non-infectious Diseases (page 440).

An outbreak of poliomyelitis caused by poliovirus type I in captive black and white colobus monkeys (Colobus abyssinicus kikuyuensis) in Kenya.

In the latter part of 1982, three black and white colobus monkeys, Colobus abyssinicus kikuyuensis, from a small breeding group maintained at the Institute of Primate Research in Kenya, became paralysed within one month. Two of these cases were fatal and the third animal survived. The clinical and pathological findings suggested a poliomyelitis-like disease. This was confirmed by the isolation of wild strains of poliomyelitis virus type I from faeces, spleen, kidney, lung and central nervous system from affected animals.

Non-suppurative encephalomyelitis in cats suggestive of a viral origin.

In 10 of 16 domestic cats with spontaneous non-suppurative encephalomyelitis, lesions were multifocal but relatively few and were considered nonspecific as to cause, although viral agents could not be excluded. Six cats had polioencephalomyelitis or polioencephalitis suggestive of viral infection. The clinical and morphological features are compared with those of previous reports of feline encephalitis possibly of viral origin. Some previously reported epidemiological and serological surveys suggest a possible role for arboviruses.