Brain and spinal cord lesions in pigs inoculated with swine vesicular disease (UKG strain) virus and coxsackievirus B5.

Pigs inoculated intravenously with swine vesicular disease virus (UKG strain), those inoculated with coxsackievirus B5, and other pigs exposed by pen contact to the same viruses developed diffuse encephalomyelitis. Perivascular cuffing, with lymphocytes and formation of neuroglia cell foci, were most prominent in telencephalon, diencephalon, and mesencephalon. Encephalitis was of mild to severe intensity. Severity of lesions was more extensive and severe in the pigs exposed to swine vesicular disease virus. Pen contact exposure to either of the 2 viruses caused a more severe central nervous system reaction than did intravenous inoculation. The type and the distribution of lesions produced by the 2 viruses indicate that they may be related.     

Immunohistochemical and histopathological study of experimental rabies infection in mice.

An immunohistochemical and histopathological study using the ABC technique was carried out to examine time-sequential virus spread in the central nervous system (CNS) of mice after inoculation with the CVS strain of fixed rabies virus by different routes; intracerebral (ic), intraocular (io), intranasal (in), intramuscular (im) and subcutaneous (sc). Only the ic and io inoculations caused fatal infections, so that detailed analysis was conducted on mice inoculated by these two routes. In ic-inoculated mice, viral antigens were detected mainly in neurons in the cerebral cortex and in the pyramidal cells and granular cells of the hippocampus. After io inoculation, viral antigen was first detected in the trigeminal nerve ganglia, following which it spreads to the cerebral cortex and cerebellum. In the hippocampus only a few cells were viral antigen-positive at the early stage after io inoculation. There were no inflammatory lesions or Negri bodies in the CNS of mice infected by either route. This suggests that clinical signs such as ataxia or depression leading to death may be due to the direct effect of the virus on the functions of neural cells, but not to inflammatory reactions. The ABC method will be useful for the early diagnosis of suspected patients or animals to have the disease when conventional histopathological and immunofluorescent antibody techniques can not detect lesions or viral antigens.     

Experimental maedi infection in sheep. 1. Detection of virus, clinical course, histopathology

Eight sheep were inoculated with Icelandic maedi strain M 88; 2 sheep served as control sheep and were in close contact with the inoculated ones. Four of the sheep were inoculated via the respiratory tract with 7×10⁶ TGID50 of strain M88 and the other 4 intracerebrally with 5×10⁵ TGID50 of the same strain.Maedi M88 strain was isolated from peripheral blood leukocytes of all inoculated sheep. There was a striking difference between the 2 groups in the appearance of demonstrable viremia after inoculation. Viremia could be demonstrated in the intrapulmonarily inoculated sheep within 2–6 months but not until 8–11 months after inoculation in the intracerebrally inoculated ones. This finding is thought most probably to reflect a weak neurotropism of the strain used. After the first demonstration of viremia, maedi virus has been recovered quite reqularly in peripheral leukocytes of all intrapulmonarily inoculated sheep, but less regularly in the intracerebrally inoculated ones. Maedi virus was isolated from 1 of the uninoculated control sheep 15 months after inoculation.The first clinical case with a clinical appearance suggesting combined involvement of maedi and visna was found among the intrapulmonarily inoculated sheep, 8% months after inoculation. Histopathological examination and virus isolation confirmed maedi. The cause of paraplegia could not be confirmed. No histopathological changes were found and no virus isolation was made from the central nervous system of this animal.One of the intracerebrally inoculated sheep died suddenly without any observed clinical signs 11 months after inoculation. Histopathological examination revealed pulmonary lesions of maedi, but no visna lesions in the central nervous system, although maedi virus was isolated from various parts of brain.None of the other experimental sheep displayed clinical signs of maedi or visna during the observation period of 18 months.     

Natural bovine lentiviral type 1 infection in Holstein dairy cattle. I. Clinical,serological, and pathological observations

Clinical, serological, and pathological abnormalities observed in Holstein cows naturally infected with bovine lentivirus 1 bovine immunodeficiency virus (BIV) and other infections were progressive and most commonly associated with weight loss, lymphoid system deficiency, and behavioral changes. Clinical evidence of meningoencephalitis was dullness, stupor, and occasional head or nose pressing postures. The polymerase chain reactions associated the BIV provirus with the lesions in the central nervous system and lymphoid tissues. Multiple concurrent infections developed in retrovirally infected cows undergoing normal stresses associated with parturition and lactation. A major functional correlate of the lymphoreticular alterations was the development of multiple secondary infections which failed to resolve after appropriate antibacterial therapy. The chronic disease syndrome in dairy cows associated with BIV may be useful as a model system for investigation of the pathogenesis of the nervous system lesions and lymphoid organ changes that occur in humans with lentiviral infection.     

Visna-maedi-like disease associated with an ovine retrovirus infection in a Corriedale sheep

A visna-maedi-like disease was found in a Corriedale sheep from which a retrovirus sharing the group antigen of visna-progressive pneumonia virus was isolated from lung, brain, and spleen. Clinically, the sheep had acute neurologic signs and dyspnea. Pathologic examination showed lesions similar to both visna and maedi. In the lung, there was a patchy interstitial pneumonia with marked lymphoid hyperplasia. Changes in the central nervous system were necrotizing nonsuppurative encephalitis of the brain stem, poliomyelitis of the cervical cord, and ependymitis and subependymal gliosis of the ventricles. Histologically, the central nervous system lesions seemed to have arisen sequentially, perhaps in response to bursts of virus replication as the agent underwent possible antigenic mutation. The severe lesions in both the central nervous system and lungs suggested a virus strain with dual tropism.     

EXPERIMENTAL ENCEPHALOMYOCARDITIS VIRUS INFECTION IN CALVES

Nine calves, were inoculated intravenously with the Innisfail strain of encephalomyocarditis (EMC) virus. Apart from a mild fever, no obvious clinical signs were noted. A low titre viraemia was demonstrated in all 5 calves from which blood was collected, and EMC virus was recovered from the myocardium of 3 of 6 calves at 2, 3 and 6 days after inoculation. Virus was not recovered from the central nervous system. No excretion of EMC virus in urine or faeces was detected in 3 calves. Histopathological lesions were present in brain tissue from only 1 calf, destroyed 14 days after inoculation, and in the heart muscle from another calf, destroyed 7 days after inoculation. Macroscopic lesions were not seen in these organs. Both neutralising and haemagglutination-inhibiting antibodies were produced within one week of infection, reached a peak in 3–4 weeks and persisted undiminished until 9 weeks after inoculation. By nitration on Sephadex G 200, it was shown that the early response was due to IgM type antibodies, and these were replaced by IgG antibody. One calf was inoculated intracerebrally with EMC virus. It developed a flaccid posterior paralysis and was destroyed 6 days later. Virus was recovered from the brain and spinal cord, but no significant histopathological lesions were detected in brain or spinal cord from this calf.     

Four distinct neurologic syndromes in Marek's disease: effect of viral strain and pathotype

A chronological study of central nervous system disorders induced by Marek's disease virus (MDV) has been conducted. Neurologic clinical signs were recorded daily for individual chickens of two genetic lines after inoculation of 13 serotype 1 MDV strains representing all three pathotypes. In addition to classical transient paralysis (TP) previously described by many workers, and acute TP, described in the companion paper, we have identified for the first time two other neurologic syndromes, persistent neurologic disease (PND) and late paralysis (LP). PND designates birds that showed a variety of neurologic signs (ataxia, torticollis, and nervous tics) after recovery from paralysis (12-15 days postin-oculation [DPI]) that either persisted through the observation period or presented a cyclic pattern. LP was a rare syndrome characterized by the late onset of the paralytic stage (about 20 DPI), perhaps indicating occasional failure of the initial intraabdominal inoculation to induce infection. Clinical signs and histopathologic alterations of the brain were also evaluated sequentially in chickens of two genetic lines after inoculation with two MDV strains (virulent MDV and very virulent plus MDV). Although clinical response differed greatly among treatment groups, types of lesions (endotheliosis, mononuclear perivascular cuffing, vasculitis, vacuolization, and increase in cellularity of the neuropil) were similar. However, early onset of lesions (by 6 days) appeared to be associated with a greater severity of clinical signs. We also found that neurologic response was greatly influenced by viral pathotype (virulence). This study thus confirms that the central nervous system is an important target organ for MDV resulting in several distinct clinical manifestations and suggests that neurologic responses in antibody-free chickens might be a useful criterion for virus pathotyping.     

Infection of Bergmann glia in the cerebellum of a skunk experimentally infected with street rabies virus.

Rabies virus is a highly neuronotropic virus and glial cell infection is not prominent in the central nervous system (CNS). Paraffin-embedded tissues from the cerebella of skunks experimentally infected with either a skunk salivary gland isolate of street rabies virus or the challenge virus standard (CVS) strain of fixed rabies virus were examined with immunoperoxidase staining for rabies virus antigen by using an anti-rabies virus nucleocapsid protein monoclonal antibody. A skunk infected with street rabies virus showed prominent infection of Bergmann glia. Although infected Purkinje cells were observed, they usually demonstrated a relatively small amount of antigen in their perikarya. A CVS-infected skunk showed many intensely labeled Purkinje cells and a relatively small number of infected Bergmann glia. These findings indicate that although rabies virus is a highly neuronotropic virus, street rabies virus strains do not always demonstrate strict neuronotropism in the central nervous system.     

Attempts to establish congenital bluetongue virus infections in calves.

Three bovine fetuses were inoculated in utero with approximately 10(3) plaque forming units of type 11 bluetongue virus. The gestational ages of the fetuses at the time of inoculation were 106, 113 and 122 days. They were spontaneously aborted 104, 65 and 109 days later, respectively, and the first and third of these fetuses were recovered. There was no grossly normal cerebral tissue, the meninges formed fluid filled sacs, and the cerebellums were reduced in size. Bluetongue virus was not isolated from the fetuses but the older one had neutralizing antibody. The three dams developed neutralizing antibody to bluetongue virus. The present work supports the observation by others that early fetal infections with bluetongue virus normally result in severe central nervous system damage and not in clinically normal, persistently infected calves.     

The response of pigs inoculated with a thymidine kinase-negative (TK-) pseudorabies virus to challenge infection with virulent virus

12 Large-White-Landrace piglets were subdivided in four groups of 3 and housed in separate units. The piglets of three groups were inoculated with the 86/27V 6C2 thymidine kinase negative (TK-) mutant of pseudorabies virus (PRV), by different routes. A second inoculation with the same mutant was given to the pigs 21 days later. The animals of a fourth group were left as uninoculated controls. 21 days following the second inoculation with the TK- mutant all pigs were challenge infected with the virulent PRV. On post challenge day (PCD) 30 all pigs were killed and samples for virus detection and histology were taken from several organs. The inoculated TK- mutant of PRV did not induce any ill effects in the pigs except a transient febrile reaction in some animals. Virus was recovered from nasal swabbings from one pig 2 days after the first inoculation of the mutant. After challenge exposure with virulent PRV, the TK- mutant-inoculated pigs were apparently protected, whereas the control pigs all were severely affected and recovered very slowly over 3 weeks. Virus was isolated from the nasal swabbings from the TK- mutant-inoculated pigs on PCDs 2 and 4, whereas the nasal swabbings from the control piglets were all positive for virus from PCD 2 through PCD 10. DNA analysis of the virus recovered showed a pattern identical to that of the virulent PRV. Histologic lesions were found in the respiratory and the central nervous systems, however, the lesions in the TK- mutant-inoculated pigs were much milder compared to those registered for the control pigs. Virus was not isolated from any of the tissue samples that were tested, but viral DNA with sequences typical of PRV genome was detected by PCR in all samples of trigeminal ganglia from either the TK- mutant-inoculated pigs or from the controls.     

Pathogenesis of Venezuelan equine encephalitis virus infection in mice and hamsters.

The pathogenesis of Venezuelan equine encephalitis (VEE) virus infection was compared in intraperitoneally inoculated mice (n = 24, 6 to 8 weeks old) and hamsters (n = 9, 90-110 g) using histopathology and immunohistochemical localization of VEE virus antigen. Infected mice developed paralysis, and the majority died by 9 days after inoculation. In contrast, hamsters did not survive beyond 3 days after inoculation, and they did not develop any neurologic signs. VEE virus antigen, demonstrated by immunoperoxidase staining, and pathologic changes were present in extraneural organs of both mice and hamsters. There was more severe involvement in hamsters, particularly in Peyer's patches of the distal small intestine. There was a severe encephalomyelitis in mice, but pathologic changes were not well established in the brains of hamsters before death. VEE virus antigen was widespread in the central nervous system of both mice and hamsters. VEE virus was found to be highly neurotropic in hamsters and had a similar distribution in the brain as in mice, but hamsters died from their extraneural disease before major central nervous system disease developed.     

鱼类病毒性神经坏死病研究现状

鱼类病毒性神经坏死病是近年来严重危害海水鱼类,引起暴发性流行的重大病害之一。目前,已知受神经坏死病毒感染的鱼类达40多种。该病毒包括4 种血清型,即红鳍东方鲀神经坏死病毒、拟鲹神经坏死病毒、条斑星鲽神经坏死病毒、赤点石斑鱼神经坏死病毒。患病鱼常表现出游泳异常,身体失去平衡等典型神经性疾病症状。病理组织学观察可见中枢神经系统特别是脑和视网膜出现严重的坏死、空泡化。病毒可通过垂直和水平两种途径传播。关于病毒的命名、感染机制及其防治还需深入研究。     

Bluetongue virus-induced hydranencephaly in cattle

Direct inoculation of bluetongue virus into 125-day bovine fetuses resulted in development of hydranencephaly. The earliest lesions after virus inoculation were a severe necrotizing encephalitis, which was most prominent in the cerebrum, and an associated nonsuppurative meningitis. At birth, the brains of infected fetuses had thin-walled cerebral hemispheres, dilated lateral ventricles, and cerebral cysts. No gross lesions were observed in the brain stem or cerebellum. Two morphologically different lesions were present in the brain of a fetus sacrificed 20 days after virus inoculation. There were discrete foci of hemorrhagic cerebral necrosis that resembled infarcts and widespread microcavitations of the intermediate and subventricular zones. Changes consistent with vascular damage were present in the brains of fetuses sacrificed 12 and 20 days after virus inoculation. Calves with bluetongue virus-induced hydranencephaly would have poor viability, but they would not be expected to have any significance as virus reservoirs.     

Relapse infection after chemotherapy in goats experimentally infected with Trypanosoma brucei: pathological changes in central nervous system

Fourteen goats were experimentally infected with Trypanosoma brucei with the following results: Four animals became terminally ill 24 to 47 days after inoculation of trypanosomes and were killed for necropsy. A second group of four goats became sick, had signs of systemic trypanosomiasis, were treated with diminazine aceturate (Berenil) and recovered showing no signs of disease over observation periods of 151 to 163 days. A third group of six goats, were treated with Berenil and temporarily recovered and in 60 to 79 days after therapy; four of these goats underwent relapse infection characterized by severe central nervous system (CNS) disease. Two of these goats were necropsied 45 days after chemotherapy, before clinical signs were evident, to show early neurological lesions. In group 3 (the relapse group), the microscopic changes became more severe as relapse infection progressed. Microscopically, the central nervous system lesions were edema, hyperemia, and infiltration of plasma cells, small lymphocytes, and some macrophages in the leptomeninges, choroid plexus, and brain parenchyma. Relapse infection is discussed from the standpoint of an occult phase of the disease where parasites are protected from the effects of trypanocidal drugs by the blood-brain barrier.     

Pathogenesis of canine parvovirus enteritis: sequential virus distribution and passive immunization studies

After oral inoculation, the sequential distribution of canine parvovirus was studied in 14 nine-week-old seronegative beagle dogs. Two or three dogs were necropsied on days 1 through 6 after inoculation. Tissues were collected for virus isolation, immunofluorescence testing, and light microscopy. Virus was isolated from, and fluorescent cells were seen in the tonsil, retropharyngeal and mesenteric lymph nodes one and two days after inoculation. Virus infection of systemic and intestinal lymphoid tissues occurred as early as three days after inoculation and was associated with viremia. Intestinal epithelial infection was first seen four days after oral inoculation. All dogs were viremic before intestinal epithelial infection was found. Fecal virus excretion first occurred four days after oral virus inoculation. Intestinal virus infection and lesions became progressively more severe between four and six days after inoculation. The severity of intestinal lesions was variable and related to the severity of systemic lymphoid tissue lesions and the magnitude and duration of viremia. Four littermates of virus-infected dogs were passively immunized against canine parvovirus with convalescent canine serum 24 hours after oral virus inoculation. Neither clinical signs, lymphopenia, nor fecal virus excretion occurred in passively immunized dogs. Intestinal epithelial infection was not demonstrable by immunofluorescence testing when passively immunized dogs were necropsied four, five, and six days after virus inoculation.     

Isolations of Cache Valley virus in Texas, 1981

Two strains of the same virus (isolates AR 168 and 7856), were isolated in 1981 from an apparently healthy cow and a sick sheep in TX, U.S.A. These isolates were shown to be members of the Bunyamwera serogroup (family Bunyaviridae, genus Bunyavirus) by complement-fixation tests. Serum dilution-plaque reduction neutralization test results indicated that the isolates are closely related to Cache Valley virus. The virus isolates were characterized by sensitivity to lipid solvent, size (50-100 nm by filtration and 70 nm by electron microscopy), heat (56 degrees C) and pH 3 lability, cytopathic effects or plaques in cultures of Vero, LLC-MK2, embryonic bovine testicle and PS cells, and pathogenicity for suckling and weaned mice by the intracranial but not the intraperitoneal route. Gnotobiotic and conventional sheep and goats were experimentally infected by inoculation with one of the isolates given either intravenously or intraperitoneally. Elevation of body temperature, depression, tremors, muscle spasms, disorientation, feeding anomalies, convulsions, or other signs of central nervous system disturbances were observed.     

Pestivirus fetopathogenicity in cattle: changing sequelae with fetal maturation

The events which followed the introduction of a heifer into a dairy herd were consistent with the animal being persistently infected with bovine diarrhoea-mucosal disease virus. Obvious damage was limited to the progeny of cows which were in the first 168 days of gestation at that time. Only fetuses up to 81 days of gestation at the putative time of introduction of infection became persistently infected in calfhood and, although they exhibited body tremor, two such calves necropsied at three months of age lacked macroscopic or microscopic lesions in the central nervous system. In contrast calves which had been more advanced in gestation, at 146 and 153 days at the time of infection, had eliminated the infection and had lesions of cerebellar dysplasia and multifocal retinal atrophy.     

Diagnosis of Transmissible Gastroenteritis in Pigs by Means of Immunofluorescence

The fluorescent antibody (FA) test for the diagnosis of field outbreaks of transmissible gastroenteritis (TGE) in baby pigs was compared to other available means including: virus isolation by inoculation of test pigs, intestinal lesions especially villous atrophy, and clinical observations.

Immunofluorescent tests were done on frozen sections of the small intestine and it was possible to make a specific diagnosis within two hours after collecting samples. The results obtained with the FA test compared favorably with virus isolation from infected tissues. It was considered a more advantageous procedure as long as infected pigs were in a relatively early phase of the disease. Because of the variability of the lesions as related to the stage of infection, pathologic diagnoses were less satisfactory. Field diagnoses made on the basis of clinical signs were least reliable.

     

Canine distemper virus-associated hypocalcemia.

A retrospective study was done to correlate serum calcium concentrations and parathyroid gland ultrastructure to clinical, immunologic, and pathologic changes experimentally induced in gnotobiotic dogs by canine distemper virus (CDV). Dogs infected with CDV had significantly reduced serum calcium concentrations associated with ultrastructural evidence of parathyroid gland inactivity, degeneration, and viral inclusions. Although CDV-infected dogs exhibited neurologic signs, minimal lesions were present in the central nervous system. It is suggested that viral-induced parathyroid dysfunction may contribute to neutrologic disturbance of CDV infection.     

Intratracheal inoculation as an efficient route of experimental infection with maedi-visna virus

Maedi-visna virus (MVV) spreads horizontally via the respiratory route. In order to establish an experimental mucosal infection route, we compared intranasal and intratracheal inoculation using the infectious MVV molecular clone KV1772-kv72/67. For intranasal infection 0.5 x 10(3)-0.5 x 10(7) TCID50 of virus was sprayed into the nostrils of the sheep. For the intratracheal infection 10(0)-10(6) TCID50 of virus was injected into the trachea. Successful infection was indicated by development of MVV specific antibodies and virus isolation over a period of 6 months. In the intranasal infection, only the sheep receiving the highest dose i.e., 0.5 x 10(7) TCID50, became infected, suggesting that intranasal application was not an efficient mode of infection. In the intratracheal infection, the sheep infectious dose 50% was 10(1) TCID50 and virus could be isolated from the central nervous system 4 months post infection with 10(4) TCID50. Therefore it is concluded that intratracheal infection is a very efficient route for experimental inoculation with MVV.