Non-purulent Meningoencephalitis Research Articles

Borna disease in an adult free-ranging Eurasian beaver (Castor fiber albicus)

Borna disease (BD) associated with a peracute bacterial septicaemia with Escherichia coli was diagnosed in an adult female, naturally infected, free-ranging Eurasian beaver of the subspecies Castor fiber albicus, clinically characterized by weight loss, depression, weakness and gurgled peristaltic sounds. The beaver was euthanized humanely. Necropsy and light microscopy revealed a non-purulent meningoencephalitis with typical mononuclear perivascular cuffs and parenchymal infiltrates. The diagnosis of BD was confirmed by detection of viral antigen and RNA by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). The PCR product was sequenced and cluster analysis revealed a close relationship between endemic clusters in Saxony-Anhalt. This is the first report of naturally occurring BD in a free-ranging Eurasian beaver.

Bovine Papillomavirus Type 1 in Brains of Cattle with a Neurological Syndrome: Pathological and Molecular Study

Bovine papillomavirus (BPV) infection is endemic in Brazilian herds. Papillomaviruses are oncogenic, with a trophic response in squamous epithelial and mucosal tissues, and are associated with asymptomatic infections, proliferative benign skin lesions (papillomas), and malignant epithelial lesions (carcinomas). The presence and expression of BPV in the blood of healthy and papillomatosis-affected cattle has been demonstrated. Experimental inoculation of Bovine papillomavirus (BPV) into calf meninges can result in meningiomas and papillomatosis, but it´s not known if its natural infection causes neoplasia and neurological syndrome in cattle. We assessed the frequency of BPV in 300 Central Nervous System (CNS) samples from cattle with neurological syndrome from several Brazilian regions obtained from surveillance of neurological syndrome. Samples were negative for rabies, Neospora caninum, BoHV-1 and BoHV-5, bovine leukemia virus, and catarrhal malignant fever (PCR). Samples were fixed in 10% buffered formalin and submitted to macroscopic examination. For histological analysis, slides were submitted to a staining protocol using hematoxylin and eosin. PCR for BPV detection was applied in CNS frozen samples using generic primers FAP59 and FAP64 (L1 gene). Thirteen (4.3%) samples were positive for BPV by PCR, with 11 of these showing no pathological changes in microscopy, and two exhibiting nonspecific non-purulent meningoencephalitis. No CNS samples showed neoplasia. Nine of the 13 BPV positive samples (69.2%) came from females and four (30.8%) from males. The 13 positive animals were age 5 to 168 months with seven over 36 months (53.8%). Five were dairy cattle, four crossbred, and three beef cattle. Only one of the 13 positive samples provided sufficient BPV DNA for sequencing, which emonstrated 99% identity to samples of BPV-1 obtained from cutaneous papillomas in cattle in Brazil. The small quantity of BPV DNA in the CNS and the low number of PCR-positive samples may be associated with low neurotropism, unspecific inflammation, or BPV-infected lymphocytes in CNS tissues or bloodstream. Natural BPV-1 infection was not associated with cerebral neoplasia or neurological syndrome.

Detection of Bovine Leukemia Virus in Brains of Cattle with a Neurological Syndrome: Pathological and Molecular Studies

Bovine leukemia virus (BLV) was investigated in the central nervous system (CNS) of cattle with neurological syndrome. A total of 269 CNS samples were submitted to nested-PCR (BLV env gene gp51), and the viral genotypes were identified. The nested-PCR was positive in 4.8% (13/269) CNS samples, with 2.7% (2/74) presenting at histological examination lesions of nonpurulent meningoencephalitis (NPME), whereas 5.6% (11/195) not presenting NPME (P > 0.05). No samples presented lymphosarcoma. The PCR products (437 bp) were sequenced and submitted to phylogenetic analysis by neighbor-joining and maximum composite likelihood methods, and genotypes 1, 5, and 6 were detected, corroborating other South American studies. The genotype 6 barely described in Brazil and Argentina was more frequently detected in this study. The identity matrices showed maximum similarity (100%) among some samples of this study and one from Argentina (FJ808582), recovered from GenBank. There was no association among the genotypes and NPME lesions.

Canine Trypanosoma evansi infection introduced into Germany

A 9-year-old male Jack Russell Terrier with a history of travel to Thailand was presented with chronic lethargy, weight loss, unilateral anterior uveitis, pancytopenia, hyperglobulinemia, and proteinuria. Numerous trypomastigotes were found on a blood smear, and using molecular methods the parasite was identified as Trypanosoma evansi. After initial response to treatment, the dog experienced a relapse with central neurologic signs 88 days after initial presentation and died. Antibodies to T evansi were detected in both serum and cerebrospinal fluid (CSF) using a card agglutination test (CATT/T evansi), and PCR analysis of CSF for T evansi was positive. Findings at necropsy included marked non-purulent meningoencephalitis. Chronic infection with T evansi in a dog that returned to Germany following international travel highlights the risk associated with introduction of foreign animal diseases to Europe and the possibility of these infections becoming endemic. Detection of chronic infection and curative therapy of trypanosomiasis are challenging, and infection is usually fatal in the dog.

TNF-Overexpression in Borna Disease Virus-Infected Mouse Brains Triggers Inflammatory Reaction and Epileptic Seizures

Proinflammatory state of the brain increases the risk for seizure development. Neonatal Borna disease virus (BDV)-infection of mice with neuronal overexpression of tumor necrosis factor-α (TNF) was used to investigate the complex relationship between enhanced cytokine levels, neurotropic virus infection and reaction pattern of brain cells focusing on its role for seizure induction. Viral antigen and glial markers were visualized by immunohistochemistry. Different levels of TNF in the CNS were provided by the use of heterozygous and homozygous TNF overexpressing mice. Transgenic TNF, total TNF (native and transgenic), TNF-receptor (TNFR1, TNFR2), IL-1 and N-methyl-D-aspartate (NMDA)-receptor subunit 2B (NR2B) mRNA values were measured by real time RT-PCR. BDV-infection of TNF-transgenic mice resulted in non-purulent meningoencephalitis accompanied by epileptic seizures with a higher frequency in homozygous animals. This correlated with lower weight gain, stronger degree and progression of encephalitis and early, strong microglia activation in the TNF-transgenic mice, most obviously in homozygous animals. Activation of astroglia could be more intense and associated with an unusual hypertrophy in the transgenic mice. BDV-antigen distribution and infectivity in the CNS was comparable in TNF-transgenic and wild-type animals. Transgenic TNF mRNA-expression was restricted to forebrain regions as the transgene construct comprised the promoter of NMDA-receptor subunit2B and induced up-regulation of native TNF mRNA. Total TNF mRNA levels did not increase significantly after BDV-infection in the brain of transgenic mice but TNFR1, TNFR2 and IL-1 mRNA values, mainly in the TNF overexpressing brain areas. NR2B mRNA levels were not influenced by transgene expression or BDV-infection. Neuronal TNF-overexpression combined with BDV-infection leads to cytokine up-regulation, CNS inflammation and glial cell activation and confirmed the presensitizing effect of elevated cytokine levels for the development of spontaneous epileptic seizures when exposed to additional infectious noxi.

Experimental induction of malignant catarrhal fever in pigs with ovine herpesvirus 2 by intranasal nebulization

Malignant catarrhal fever (MCF), a frequently fatal herpesviral disease primarily of ruminant species, has been sporadically reported in pigs. All cases of naturally occurring porcine MCF reported to date have been linked to ovine herpesvirus 2 (OvHV-2), a gammaherpesvirus in the genus Macavirus carried by sheep. Experimental induction of MCF by aerosolization of the virus in nasal secretions collected from infected sheep has been successful in bison, cattle and rabbits. The goals of this study were to determine the susceptibility of pigs to MCF following experimental intranasal inoculation of OvHV-2, and to characterize the disease. Twelve pigs in four groups were nebulized with 105, 106, 107, or 108 DNA copies of OvHV-2 from sheep nasal secretions. Three control pigs were nebulized with nasal secretions from uninfected sheep. Three additional pigs were inoculated intravenously with 107 DNA copies of OvHV-2 to evaluate this route of infection with cell-free virus. Seven of twelve intranasally challenged pigs became infected with OvHV-2. Five of these seven, all in higher dose groups, developed MCF. Lesions resembled those reported in natural cases of porcine MCF. The most striking and consistent histological lesions were in trachea, lung, kidney and brain. These comprised mucopurulent tracheitis, interstitial pneumonia, necrotizing arteritis–periarteritis, and nonpurulent meningoencephalitis. No infection was established in the intravenously challenged or control groups. The study showed that MCF can be experimentally induced in pigs by aerosol challenge using sheep nasal secretions containing OvHV-2. Domestic pigs are a natural clinically susceptible host for sheep-associated MCF. They represent a useful, cost-effective model for MCF research.

First Report on the Frequency and Molecular Detection of Neuropathogenic EHV-1 in Turkey

There has been an increase in outbreaks of neuropathogenic equine herpesvirus-1 (EHV-1) in the United States and Europe. However, the presence and frequency of neuropathogenic EHV-1 in Turkish horses are not known at present. This study aimed to investigate the frequency of EHV-1 and neuropathogenic strains of EHV-1 in the Marmara Region of Turkey. Samples were analyzed for the presence of EHV-1 and neuropathogenic EHV-1 by real-time PCR TaqMan probe assays. Overall detection rate of EHV-1 was 45.5% (51 of 112). The detection rates were 70.5% (24 of 34) in aborted fetuses, 53.3% (8 of 15) in neonatal deads, 66.6% (4 of 6) in foals, 40% (2 of 5) in dead mares, and 25% (13 of 52) in living mares. Overall detection rate of neuropathogenic EHV-1 was 7.8% (4 of 51), and the real-time PCR results were confirmed by sequencing. Neuropathogenic strains of EHV-1 were detected in the brain and lung of two mares with neurological disease but without a history of abortion, in the brain of a foal that died of respiratory disorder, and in the nasal swab from a mare with a history of abortion. On histopathology, nonpurulent meningoencephalitis, hemorrhages, and vasculitis were seen in the brain. In conclusion, results of this study indicated, for the first time, that the neuropathogenic EHV-1 is circulating in the Marmara Region of Turkey. The results of this study also show that the current risk for non-neuropathogenic strains is high, whereas risk for the neuropathogenic EHV-1-G2254 strain seems to be low. As outbreaks of EHV-1 continue in the Marmara region of Turkey, surveillance for neuropathogenic EHV-1 genotype should be maintained.

Maedi-Visna virus infection in a Merino lamb with nervous signs

A Maedi-Visna virus (MVV) infection was diagnosed in a 10-month-old lamb from a Turkish flock. The animal suddenly showed nervous signs and died within 2 days. At necropsy, different pulmonary and nervous lesions were observed. A Coenurus cerebralis cyst was also present in the right-brain hemisphere. Severe nonpurulent meningoencephalitis and lymphoproliferative pneumonia were detected by histopathology. MVV proviral DNA was demonstrated by polymerase chain reaction (PCR) in formalin-fixed and paraffin-embedded samples collected from the brain and the lungs. This unusual report in a young animal confirms that not only adult sheep but also lambs can develop MVV disease. The hypothesis that concurrent nervous and pulmonary diseases increase the severity of the lesions due to MVV and reduce the incubation time should be better evaluated.

Transmission of Ovine Herpesvirus 2 from Asymptomatic Boars to Sows

To the Editor: Malignant catarrhal fever (MCF) is an often lethal viral disease of susceptible biungulates from the Bovidae, Cervidae, and Suidae subfamilies. MCF in pigs has been associated with direct or indirect contact with sheep, which are the main reservoir of ovine herpesvirus 2 (OvHV-2) (1). A recent report detected infected but asymptomatic swine in the absence of known exposure to sheep or goats (2). Porcine MCF is difficult to diagnose because of its nonspecific clinical signs and sporadic nature; however, an outbreak involving 41 swine has been described (3). Pigs are terminal hosts and are not believed to spread the virus. Here we describe OvHV-2 DNA in the blood and semen of asymptomatic boars and from the brain of symptomatic sows and gilts with MCF that was probably transmitted by artificial insemination. The MCF cases occurred on two 3-site commercial farms with 2,700 and 1,670 sows in 2 different counties in southwestern Brazil. No MCF losses previously had been recorded in the region, and the animals had no known direct or indirect contact with sheep. The 2 farms had high biosecurity. The first case was recorded in September 2004, and the number of cases increased in July 2006. Twenty-eight sows and gilts, 20 of them pregnant and at >25 days’ gestation, died during January 2007–March 2008, when the last case was observed. Clinical features in sows and gilts were depression followed by abortion, fever (41°C), and anorexia. After the onset of clinical signs, neurologic symptoms developed such as ataxia, tremors, convulsions, and aggressive behavior. Animals that survived longer showed forelimb paralysis, stood in a dog-sit position, and gnawed with abundant salivation on pen bars. Specimens from randomly selected dead sows and gilts from the outbreaks during 2004–2008 were obtained for histopathologic examination, immunofluorescence testing for rabies virus, viral and bacterial isolation, and PCR. No bacterial or viral growth was detected, and direct immunofluorescence for rabies virus was negative. Microscopic examination showed high-grade nonpurulent meningoencephalitis characterized by lymphocytic cuffings with vasculitis in the brain hemisphere, the brainstem, the spinal cord, and, to a lesser extent, the cerebellum. Multifocal areas of edema, fibrinoid necrosis, and lymphocytic infiltration also were observed (Figure). OvHV-2 DNA was detected by using a specific PCR (4) in 5 of 7 paraffinized sections of the brainstem (5). To analyze the possible presence of other porcine lymphotropic herpesviruses in samples that reacted positively for OvHV-2, a nested PCR with degenerate primers (6,7) was applied. None of the OvHV-2–positive samples reacted positively for porcine lymphotropic herpesviruses. To confirm that the virus was a member of the MCFV group, we purified 1 amplicon and submitted it for automated sequencing. This nucleotide sequence was deposited in GenBank under accession no. {type:entrez-nucleotide,attrs:{text:HQ223415,term_id:313495121,term_text:HQ223415}}HQ223415, and it showed 99% identity with previously deposited OvHV-2 sequences. Figure Brainstem of a sow with vasculitis that was associated with ovine herpesvirus 2, showing edema, necrosis (fibrinoid necrosis), and infiltration of lymphocytes in the adventitia of the artery. Severe perivascular (Virchow-Robin space) lymphocytic cuffing ... To find possible carriers of the virus, blood samples were collected from 9 pregnant sows, 10 nonpregnant sows, and 30 breeding boars and analyzed for OvHV-2 DNA. Samples from 3 boars were positive. Nasal swabs and semen samples were collected from these infected boars to investigate the potential mode of OvHV-2 transmission, and OvHV-2 DNA was detected only in semen samples. Two of the 3 semen samples had >350 copies/2 µg of total DNA, suggesting that these animals shed virus (8,9). During this period, all infected boars remained clinically healthy. In Brazil, porcine MCF has been found primarily in pregnant sows and gilts. Our findings of OvHV-2 DNA in the semen of asymptomatic boars suggest that the OvHV-2 in the sows and gilts originated from asymptomatic boars that were responsible for maintaining the virus in the herd. Whether virus shedding in the semen was temporary or lasted for a long period is not known. Emergence of OvHV-2 in boars that had no known contact with sheep was surprising, especially given the possibility of venereal transmission through contaminated semen. The occurrence of OvHV-2 infection in other specific pathogen–free farms is unknown, and it is not possible to suggest a strategy to guarantee OvHV-2-free herds.

Borna Disease in an Adult Alpaca Stallion ( Lama pacos)

Borna disease (BD) was diagnosed in a 2-year-old male alpaca with a history of chronic suppressed sexual desire and acute stretching convulsions. Microscopical examination of the central nervous system revealed non-purulent meningoencephalitis with mononuclear perivascular cuffing. The diagnosis was confirmed by immunohistochemistry, in-situ hybridization, polymerase chain reaction (PCR) and sequencing of PCR products and alignment with known Borna disease virus sequences. Serological screening of the herd was performed. This is the first detailed report of naturally occurring BD in alpacas.

Restricted expression of Borna disease virus glycoprotein in brains of experimentally infected Lewis rats

Borna disease virus (BDV) induces a persistent infection in the central nervous system (CNS) accompanied by a non-purulent meningoencephalitis. BDV-infection of Lewis rats provides an important model to investigate basic principles of neurotropism, viral persistence and resulting dysfunctions. To date, the in vivo strategies of BDV to persist in the CNS are not fully understood. Viral glycoproteins are main targets of the antiviral defence implicating a controlled expression in case of persistent infections. Therefore, we analysed the expression profiles of the BDV-glycoprotein (BDV-GP) and corresponding BDV-intron II RNA in experimentally infected rat brains, focusing on their spatio-temporal occurrence, regional, cellular and intracellular locations. This was carried out by immunohistochemistry and in situ hybridization. The expression pattern of the most abundantly expressed BDV-nucleoprotein (BDV-N) served as a reference. BDV-N mRNA was detected preferentially in the cytoplasm of neurones, whereas BDV-intron II mRNA was found predominantly in the nucleus of brain cells. The genomic RNA was restricted to the nucleus. Expression of BDV-GP was significantly lower than BDV-N expression and mainly limited to cerebral cortex, hippocampus, amygdala and thalamus. BDV-GP was restricted to larger neurones; BDV-N occurred also in astrocytes, oligodendrocytes and ependymal cells. The expression profiles of BDV-GP, BDV-N and their mRNAs are significantly different, indicating that BDV-GP expression is regulated in vivo. This might be achieved by restricted nuclear export and/or maturation of BDV-intron II mRNA or limited translation as a viral mechanism to escape from the immune response and enable persistence in the CNS.

Neuropathologic Study of Experimental Classical Swine Fever

The aim of this study was to report on the lesions occurring in the central nervous system (CNS) during experimental classical swine fever (CSF) to clarify the spatial and chronologic distribution of the lesions and virus antigen in the CNS. To learn more about the pathogenetic mechanisms of the lesions during CSF in the CNS and to investigate the role of the virus in these mechanisms, cellular infiltrates and infected cells have been characterized. Twenty-eight pigs were inoculated with the virulent CSF virus isolate Alfort 187 and slaughtered from 2 to 15 postinoculation days; 4 animals of similar background served as a control group. Immunohistochemistry, electron microscopy, and the transferase-mediated deoxyuridine triphosphate nick-end labeling method were used to detect viral antigens and apoptosis. The results showed the presence of nonpurulent meningoencephalitis, occasional microhemorrhages, and apoptosis of the lymphocytes forming the perivascular and interstitital infiltrate in swine with CSF. Macrophages appeared to display little involvement in CNS lesions. The infected cells observed at the early stage of disease were lymphocytes and microglial cells in the rostral portion of the telencephalon, with infection of these cells in other areas in the next stages. The relationship between these lesions and the presence of viral antigen varied according to the type of lesion: hemorrhages were not associated with the presence of antigen in endothelial cells, but infiltrate-cell apoptosis was temporally and spacially associated to viral infection. However, the link between viral infection and the presence of cell infiltrate was far from clear.

Expression of allograft inflammatory factor‐1 and haeme oxygenase‐1 in brains of rats infected with the neurotropic Borna disease virus

Experimental infection of Lewis rats with Borna disease virus (BDV) causes an immune-mediated nonpurulent meningoencephalitis. Viral persistence in the central nervous system is accompanied by mononuclear infiltrates, activated monocytic/microglial cells and reactive astrocytes. The immune-mediated process was further characterized by expression analysis of allograft inflammatory factor-1 (AIF-1), a novel marker of monocyte/microglial activation and of glial fibrillary acid protein (GFAP) between day 3 and day 50 post infection (p.i.). Potential neuroprotective effects of these cells were studied by the induction of haeme oxygenase-1 (HO-1), a defensive molecule against oxidative stress in various brain insults. In BDV-infected rat brains, mononuclear infiltrates and AIF-1 expression increased up to day 28 p.i. During early time points p.i., AIF-1 expression was mainly found in inflammatory lesions and adjacent brain parenchyma. Already 24 days p.i., a widespread upregulation of AIF-1 was observed which declined only moderately beyond day 28 p.i. HO-1 induction was maximal between days 18 and 28 p.i. Increased amounts of GFAP-positive astrocytes were present beyond 24 days p.i. Viral antigen expression increased simultaneously to the inflammatory reaction and persisted up to 50 days p.i. Widespread upregulation of AIF-1 indicates an early, long-lasting microglial activation, which might be involved in the immunesurveillance of the immune-mediated inflammatory events. The early peak of HO-1 most likely represents a neuroprotective, anti-inflammatory response by invading monocytes, microglial cells and astrocytes during the formation of encephalitic lesions and acute viral replication.

Clinicopathologic observations on Coenurus cerebralis in naturally infected sheep

Twelve sheep from 7 different flocks consisting of approximately 150-250 animals each were diagnosed with coenurosis caused by the larval stage of Taenia multiceps. Ataxia, incoordination, drowsiness, hind leg paralysis and coma were the most prominent clinical symptoms. Monocytosis and lymphocytosis were observed upon hematological examination. Creatin kinase (CKBB) levels of the animals varied between 421 and 495 U/l. Cysts were commonly localized in the parietal and frontal lobes of the brain and in the cerebellum. In two cases, cysts were found on the lumbar aspect of the medulla spinalis. Symptoms were related to cyst localization. Depression, tilting of the head either to the right or left and head pressing were seen when cysts were located in the cerebrum. Incoordination and hyperexcitability were noted if the cysts were involved with the cerebellum and when located in the spinal cord, hind leg paralysis was the typical clinical sign. On microscopic examination, atrophy was observed in the central nervous system (CNS) organs due to pression by the bladderworms. Nonpurulent meningoencephalitis with perivascular cuffings were the most common histopathological findings. In periodic acid Schiff staining (PAS), positive reaction was observed in protoscoleces. Neurons were the most affected cell type when stained by the Klüver Barrera method. This method also showed that in the CNS, Coenurus cerebralis caused a prominent glial reaction. When parasites were localized in the nervous system treatment was impossible. Animals without neurologic sings were treated with praziquantel (Tenikur tablet-Topkim A.S.) 50-100 mg/kg/day for three days.

Characterization of Lesions Caused by a South American Virulent Isolate ('Quillota') of the Hog Cholera Virus

In this study, macroscopic and histopathological lesions produced by a virulent South American isolate ('Quillota') of hog cholera virus were studied. The virus was inoculated in doses of 10(5)TCID50 in each of 35 pigs of 20 kg live weight. The animals were slaughtered from 4 to 18 days post-inoculation. The presence of virus antigens in lymphatic tissue was confirmed by both direct immunofluorescence and Avidin-Biotin-Peroxidase techniques in formalin-embedded tissue samples. Histological sections were stained with haematoxylin-eosin and Mallory's phosphotungstic acid haematoxylin methods. The 'Quillota' isolate used in this study caused a disease characterized by vascular lesions (splenic infarcts, haemorrhages in the lymph nodes and the urinary system and disseminated microthrombosis), and necrosis of lymphocytes, particularly in the B-areas of the lymphoid organs, lesions that are characteristic of the acute form of the disease. Other lesions observed were a non-purulent meningoencephalitis, the necrosis of the epithelial cells of tonsils, the presence of fibrin nets in the red pulp and a marked thickening of the alveolar septa.

Distribution of Borna disease virus in the brain of rats infected with an obesity-inducing virus strain.

Experimental infection of Lewis rats with Borna disease virus (BDV), a nonsegmented, single-stranded RNA virus, usually causes an immune-mediated biphasic neurobehavioral disorder. Such animals develop a persistent infection of the CNS with viral antigen expression in all brain regions and a disseminated nonpurulent meningoencephalitis. Interestingly, intracerebral infection of Lewis rats with a BDV-variant (BDV-ob) causes a rapid increase of body weight with the development of an obesity syndrome without obvious neurological signs. The obese phenotype is correlated with a characteristic distribution of inflammatory lesions and BDV-antigen in the rat brain. Infiltration with mononuclear immune cells and viral antigen expression are restricted to the septum, hippocampus, amygdala and ventromedian tuberal hypothalamus. Therefore, infection with the obesity-inducing BDV-ob results most likely in neuroendocrine dysregulations leading to the development of an obesity syndrome. This might be due to the restriction of viral antigen expression and inflammatory lesions to brain areas which are involved in the regulation of body weight and food intake. The BDV-induced obesity syndrome represents a model for the study of immune-mediated neuroendocrine disorders caused by viral infections of the CNS.

Neonatal Multifocal Encephalomalacia and Other Lesions in the Brains of Georgia Chicks: 1991-95

Outbreaks of neonatal multifocal encephalomalacia with sepsis have been reported among flocks of very young chicks in Belgium, Scotland, and the United States. The purposes of the present study were to describe intralesional bacterial cocci in chicks with this type of encephalomalacia and to determine its incidence during 1991-95, and to determine the importance of this lesion with respect to the frequency of all other brain lesions/ diseases during the same time period. All laboratory records of broiler chickens examined at the Georgia Poultry Laboratory from Jan. 1, 1991, through Dec. 31, 1995, where the histopathologic diagnoses included the letter string *encephal* were retrieved for further study. The leading etiology for brain disease was nutritional encephalomalacia (57%), followed by neonatal encephalomalacia (22%), septic meningoencephalitis (16%), and Marek's disease (14%), in turn followed by nonpurulent encephalitis (7%), avian encephalomyelitis (3%), and mycotic meningoencephalitis (3%). Diagnosis of neonatal multifocal encephalomalacia with sepsis in the brains of Georgia chicks is a perennial one. Microscopically, the condition is characterized by mild to maximal multifocal locally extensive fibrin thrombosis of blood capillaries, and necrosis (encephalomalacia, malacia) of surrounding zones of brain stem and/or cerebral hemisphere neuropile. In 44% of cases of neonatal encephalomalacia fibrin thrombosis of blood capillaries was accompanied by intralesional gram-positive coccoid bacteria that were most abundant in medium- and small-sized arterioles or venules. Only gram-positive coccoid bacteria are found in cases of neonatal encephalomalacia (P < 0.05), and only gram-negative rod-shaped bacteria are found in cases of septic meningoencephalitis (P < 0.05). Therefore, bacterial culture and routine light microscopic histopathology are sufficient for diagnosing the condition when the differential diagnosis for neurologic disease in chicks includes neonatal encephalomalacia.

Determination of immune cells and expression of major histocompatibility complex class II antigen in encephalitic lesions of experimental Borna disease

After intracerebral infection with Borna disease virus adult Lewis rats develop a virus-induced immunopathological reaction resulting in severe neurological symptoms and a non-purulent meningoencephalitis. The composition of inflammatory cells and major histocompatibility complex (MHC) class II antigen expression during the course of the infection was investigated using immunocytochemistry with a panel of monoclonal antibodies (mAb). Macrophages and lymphocytes of the T helper phenotype (CD4+) were dominant at all stages of infection, whereas T suppressor/cytotoxic lymphocytes (CD8+) were less frequent. B lymphocytes and plasma cells occurred mainly during later stages of the disease and marked parenchymal deposition of immunoglobulin developed. Beginning 10 days after infection massive expression of MHC class II antigen was noted up to the termination of experiments 70 days after infection. Besides lymphatic cells and macrophages, cells morphologically resembling microglia expressed this antigen. Furthermore, ependymal cells were found positive for MHC class II expression during infection whereas astrocytes remained negative. These findings are consistent with previous results which provide evidence for a delayed-type hypersensitivity reaction being operative in the pathogenesis of Borna disease.

Bovine herpesvirus 1: molecular and antigenic characteristics of variant viruses isolated from calves with neurological disease.

This report presents data showing that several virus isolates recovered in Argentina, mainly from calves with non-purulent meningo-encephalitis, represent a hitherto unrecognized antigenic variant of BHV-1. The following experimental approaches have been adopted to demonstrate both the unique features among and the relatedness with BHV-1 of these isolates: i) crossed serum neutralization test with rabbit immune sera, ii) analysis by SDS-polyacrylamide gel electrophoresis of radio-labeled virus induced polypeptides and glycoproteins, iii) discriminating reactivity of a panel of monoclonal antibodies which recognize known virus types, and iv) restriction endonuclease analysis of viral DNA. Another strain of BHV-1, which exhibits a specific neuropathogenic potential [Hall et al., Austral. Vet. J. 42, 229-237 (1966)] shares all major features with the viral strains originating from Argentina. Our results imply that antigenic variants of BHV-1 exist and that they can be accurately and easily identified and differentiated by the available methods.

Some Pathogenetic Aspects of Borna Disease

Publisher Summary Borna disease (BD) is a chronic encephalomyelitis occurring naturally in horses and sheep. It is characterized by a long incubation period and a progressive development with gradual loss of coordination and certain sensory afflictions. Histopathological lesions are only seen in the nervous system. In the CNS they are characterized by non-purulent meningoencephalitis and myelitis. Perivascular infiltrations in the grey matter are the main changes observed. A necrotizing encephalitis is rarely seen. Some indications on pathogenesis of BD have been obtained in experimentally infected rabbits (unpublished results). Virus specific antigen becomes detectable about 12 days after immune comples (IC) inoculation. This can be seen in the cortex and olfactory bulbs. It spreads to other areas of the brain including the hippocampus, midbrain, and cerebellum. Neurons in the retina, trigeminal ganglia, and the autonomic ganglia also have antigen in the late infection. In addition, cells of the adrenal medulla are also infected.