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H E Webb

Publications and source records attributed to H E Webb.

At least 55 records · Page 3Linked to original sources

An ultrastructure study of cerebellar lesions induced in mice by three inoculations of avirulent Semliki forest virus.

An ultrastructural study of cerebellar lesions involving axonal and myelin degeneration induced in adult Swiss A2G mice by 3 intraperitoneal inoculations of avirulent Semliki Forest virus is described. Cerebellar white matter samples examined by light and electron miscroscopy 21 days after the first virus infection revealed microcystic areas, degenerating axons, macrophages containing myelin debris as well as normal elements. By light microscopy foci of myelin loss were apparent. At 28 days groups of degenerating axons were apparent in the white matter. No virus was seen in any of the sections.

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An electron-microscopic study of avirulent and virulent Semliki forest virus in the brains of different ages of mice.

Ultrastructural studies of brains infected with avirulent and virulent strains of Semliki forest virus (SFV) were performed in 2-7, 14, 19, and 21-28 day old mice. Mature virus particles, dense clumps of fine granules, spherules and advanced stages of viral development i.e. cytopathic vacuoles, Type II (CPV II) are seen in the brains at all ages with the virulent strain which is pathogenic to all age group of mice. In the avirulent strain infection which is pathogenic to mice below 15 days old, no mature virus particles or advanced stages of viral development are seen in 19 day old and adult mice in spite of high virus titres. However, dense clumps of fine granules and spherules are seen which seem to have the capacity to develop into lethal highly infectious mature virus when reinoculated into 2-7 day old mice. It is suggested that the dense clumps of fine granules and spherules are very early viral forms, which are seen in all age groups of mice. The cut-off mechanism in pathogenicity of the avirulent strain occurs in mice around 14 days old. Though some mature virus particles and advanced viral developmental stages are seen in these mice they were much less frequent compared to baby mice. Lymphoblastic type cells are numerous in this age group. These cells are seen more frequently in all ages of mice infected with the avirulent strain as compared to the virulent strain. These mononuclear cells can have an immunological role and may play a part in limiting the process of viral maturation and hence preventing death. Polymorphs and macrophages are rare with the avirulent infection but are the predominant infiltrating cells in the virulent strain infections. With the avirulent infections the astrocytes show hypertrophy and intranuclear inclusions are seen in them.

Age Factors↗

Virus-associated demyelination. A model using avirulent Semliki Forest virus infection of mice.

Lesions produced by the infection of Swiss/A2G mice with a single inoculation of an avirulent strain of Semliki forest virus have been studied by light and electron microscopy. Whilst a mild encephalitis was detected in the great majority of mice infected, focal areas of myelin loss were observed in the cerebellar white matter of only 25% of cases. The incidence of myelin loss in other strains of mice ranged from 21% in BSVS mice to 8% in SJL/J mice. The possible mechanisms involved in the pathogenesis of the myelin loss are discussed.

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The pathogenesis of avirulent Semliki Forest virus infections in athymic nude mice.

The course and outcome of intraperitoneally induced infections with the avirulent strain A7(74) of Semliki Forest virus have been studied in athymic 'nude' (nu/nu) mice, their heterozygous (nu/ + ) littermates and conventional Swiss A2G mice. The main distinguishing characteristics of the infection in the nu/nu mice were the persistence of virus in the brain after an initial phase of incomplete virus clearance and the apparent establishment of a secondary phase of virus replication in the brain which was associated with a falling neutralizing antibody response. This secondary phase of virus replication persisted until at least the 28th day after inoculation. In addition the typical histological lesions of encephalitis induced by this virus were rare and focal demyelination, which occurred at a light microscopy level in up to 26% of nu/ + and Swiss A2G mice, was not observed. It is suggested that in immunocompetent mice the development of lesions including demyelination may be a result of an immunopathological response to virus infection which is related to the presence of thymus derived lymphocytes.

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Brain lysosomal glycosidase activity in immunosuppressed mice infected with avirulent Semliki forest virus.

Mice infected with an avirulent strain of Semliki forest virus show an increase in the activity of some of the brain lysosomal glycosidases. The increase in activity of these enzymes has been correlated with the histological, virological, and serological changes that result from the infection in the presence and absence of immunosuppression. Semliki forest virus alone caused the development of a mild encephalitis with perivascular infiltration, microgliosis, astrocyte hypertrophy, and a focal spongiform encephalopathy, together with an increased activity of brain N-acetyl-beta-D-glucosaminidase and beta-glucuronidase. Antilymphocyte serum given after infection marginally affected the course of the disease. Cyclophosphamide markedly delayed the development of the spongy changes in the increase in enzyme activities, but not the perivascular infiltration. It is suggested that the increased activity of the lysosomal glycosidases studied may be linked both to the development of a successful immune response and to the focal spongiform changes produced by the infection.

Acetylglucosaminidase↗

Demyelination in mice after two or three infections with avirulent Semliki Forest virus.

Adult mice given two or three intraperitoneal inoculations with avirulent Semliki Forest Virus showed typical lesions of a viral encephalitis similar to those caused by a virulent strain of the virus. Demyelination also was seen in the medulla and in the folia of the cerebellar white matter. Neuronophagia was seen only in mice that had had three successive infections. The repeated inoculations of avirulent virus exacerbates the encephalitis of a single inoculation and causes demyelination. The mice did not have neurological clinical signs except for a short-lived weakness of the hind legs. No central nervous system lesions were seen by the 7th and 8th week after the initial infection and all mice recovered.

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The effect of irradiation on demyelination induced by avirulent Semliki Forest virus.

A dose of 500 rad total body irradiation before Semliki Forest virus infection was the most effective in producing multiple foci of demyelination in Swiss mice. Animals receiving this dose had the highest virus titre of Semliki Forest virus persisting in the brain and a delayed antibody response. In spite of extensive demyelination no obvious clinical signs such as paralysis were observed.

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An electron-microscopic study of the development of virulent and avirulent strains of Semliki forest virus in mouse brain.

Two strains of Semliki Forest Virus (SFV), the avirulent and virulent, were used to study the development of virus in both baby and adult mouse brain. The development of SFV in the brain was similar in baby and adult brain using the virulent strain and in the baby mouse brain using the avirulent strain. Mature virus could not be found in adult mouse brain using the avirulent strain. This paper shows that extracellular virus particles near the cell membrane stimulate the formation of coated vesicles and thus absorption of virus particles by the cell. It is suggested that these coated vesicles with contained virus particles are stimulated to develop nucleoid cores on their membrane forming cytopathic vacuoles, Type II (CPV-II). Excessive membrane growth takes place and the membrane of the CPV-II with the nucleoid cores invaginates to form intravacuolar tubules. It is suggested that these tubules become responsible fro the formation of mature virus particles. Thus the membrane of the CPV-II appears to be responsible for the development of both the inner core and outer coat of the virus.

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Effect of an inapparent viral encephalitis on the levels of lysosomal glycosidases in mouse brain.

The changes in the activity of several lysosomal glycosidases of mouse brain which occured during an inapparent infection with the A774 strain (avirulent) of Semliki Forest Virus (SFV) have been related to the histopathological and viral changes caused by the disease. N-acetyl-beta-D-glucosaminidase, N-acetyl-beta-D-galactosaminidase and beta-glucuronidase were significantly elevated between post-inoculation day 7 and 28. Lesions characteristic of encephalitis were also observed between these times. Histochemical and biochemical of encephalitis were also observed between these times. Histochemical and biochemical observations showed that not all areas of brain were affected equally; the cerebellum, parts of the mid-brain and the spinal cord showed the most sevre biochemical and histochemical changes, whilst histopathological lesions were more evenly distributed. The biochemical results have been related to the histological, histochemical and virological findings and the production of glycosidases from 2 or more cellcular types has been postulated.

Acetylglucosaminidase↗

Enhanced resistance of mice to infection with Langat (TP21) virus following pre-treatment with Sindbis or Semliki forest virus.

Significant protection to heterologous i.c. challenge with the flavovirus Langat occurred after a single i.c. injection of avirulent strains of the alpha viruses Semliki Forest or Sindbis given 1 day to 5 weeks before challenge. Some protection also occurred after an i.p. infection with these viruses. We consider that the protection afforded by the alpha viruses is due to interference with the multiplication of Langat virus and is related to the maximum level of brain infectivity reached in the alpha virus infection.

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Motor activity changes in scrapie-affected mice.

Measurements of spontaneous motor activity using Animex equipment have been made throughout the incubation period in mice developing scrapie. A progressive fall in activity has been noted from an early stage in the disease process well before clinical signs of scrapie were evident. The initial fall was followed by an upsurge in activity at about the time when clinical signs of disease develop.

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Mouse hydrocephalus and encephalitis following intracerebral infection with Newcastle disease vaccine viruses.

Hydrocephalus and encephalitis in 14-day-old mice was induced by an intracerebral inoculation of a high dose of live Newcastle disease vaccine viruses. The distended lateral ventricles occurred as a result of aqueduct stenosis superimposed on ciliary degeneration and destruction of ependymal cells. The brain virus titres were high on Days 3, 5 and 7 but never exceeded the titre of the original dose given. Positive serum haemagglutination-inhibition titres persisted throughout the experiment.

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