ABSTRACT
Infections with the avirulent (A7/74) strain of Semliki Forest virus which causes primary demyelination of the central nervous system in mice have been studied further in nude athymic (nu/nu) mice and their immunocompetent (nu/+) litter mates to measure the production of immunoglobulins. This has been done by radial immunodiffusion and enzyme-linked immunosorbent assays. Half the nude mice examined were able to synthesize specific IgG but at levels 1,000-fold lower than their nu/+ littermates. The majority of nude mice reconstituted with spleen cells from nu/+ mice 1 day before infection with virus were able to synthesize specific IgG nearly as well as the nu/+ animals.
Subject(s)
Demyelinating Diseases/immunology , Immunoglobulin G/biosynthesis , Semliki forest virus/immunology , Togaviridae Infections/immunology , Animals , Antibody Specificity , Enzyme-Linked Immunosorbent Assay , Female , Immunodiffusion , Immunoglobulin M/biosynthesis , Male , Mice , Mice, NudeABSTRACT
Four-week-old mice were infected intraperitoneally with an avirulent strain A7(74) of Semliki Forest virus (SFV) and killed at 4, 10, 15, 21 and 29 days after inoculation. Focal demyelinating lesions were present by 10 days. These were usually accompanied by a mononuclear infiltrate which included lymphocytes possessing characteristic cytoplasmic projections. These latter extended deep into the cytoplasm of adjacent cells, which were usually astrocytes and macrophages. Other features of the focal lesions were expansion of the extracellular space and demyelination which appeared to be fragmentation or lysis rather than stripping of myelin by macrophages. Although healing occurred in some mice after 4 weeks, acute lesions were still found in others of the same age. It was concluded that the demyelination probably had an immunological basis, and interaction between elements of the immune system and glial cells was a factor which inhibited orderly remyelination of the relatively mild lesions resulting from this infection.
Subject(s)
Brain/ultrastructure , Demyelinating Diseases/pathology , Togaviridae Infections/pathology , Animals , Astrocytes/ultrastructure , Lymphocytes/ultrastructure , Male , Mice , Microscopy, Electron , Myelin Sheath/ultrastructure , Semliki forest virusABSTRACT
Mice from the following strains--Simpson, SWR/J, TO, CBA/Ca, CW (outbred), LAC/G (outbred), SJL/J and Swiss A2G (outbred)--were infected i.p. with avirulent Semliki Forest virus. Clinical signs of disease were noted, histopathological changes assessed and the blood and brain virus infectivities and serum immunoglobulin levels were measured. Only the CW, TO and Swiss/A2G animals showed convincing evidence of demyelination at the light microscopy level but all strains developed encephalitis and microcystic (spongiform) lesions.
Subject(s)
Demyelinating Diseases/etiology , Encephalitis/etiology , Mice/microbiology , Semliki forest virus/pathogenicity , Animals , Demyelinating Diseases/immunology , Demyelinating Diseases/microbiology , Encephalitis/immunology , Encephalitis/microbiology , Female , Immunoglobulin G/analysis , Male , Mice, Inbred Strains/microbiology , Togaviridae Infections/immunologyABSTRACT
The amount of virus in macrophages from normal mice infected in vivo and in vitro with avirulent Semliki Forest Virus A7(74)C1 and virulent L10/C1 has been compared to that in macrophages infected similarly from mice given Myocrisin (colloidal gold) before inoculation. Very high titres of virus were found in all macrophages which had been "blockaded" with Myocrisin up to 10(8.5)/ICLD50/ml with the avirulent strain and up to 10(7.2)/ICLD50/ml with the virulent strain. "Blockade" of the macrophages in this way made the normally avirulent strain virulent. The possible reasons for this are discussed.
Subject(s)
Arbovirus Infections/microbiology , Macrophages/microbiology , Animals , Arbovirus Infections/immunology , Blood/microbiology , Brain/microbiology , Gold Sodium Thiomalate/pharmacology , Mice , Semliki forest virus/isolation & purification , Time Factors , Virulence/drug effectsABSTRACT
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.
Subject(s)
Arbovirus Infections/pathology , Semliki forest virus/pathogenicity , Animals , Antibodies, Viral/biosynthesis , Arbovirus Infections/immunology , Arbovirus Infections/microbiology , Blood/microbiology , Brain/microbiology , Brain/pathology , Female , Male , Mice , Mice, Nude , Semliki forest virus/isolation & purification , Species Specificity , VirulenceABSTRACT
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.
Subject(s)
Brain/pathology , Demyelinating Diseases/etiology , Encephalitis/etiology , Semliki forest virus/pathogenicity , Animals , Brain/ultrastructure , Demyelinating Diseases/pathology , Encephalitis/pathology , Mice , Mice, Inbred BALB C , Mice, Inbred CBA , Mice, Inbred Strains , Mice, Nude , Species SpecificitySubject(s)
Encephalitis/pathology , Scrapie/pathology , Virus Diseases/pathology , Acetylglucosaminidase/metabolism , Animals , Brain/pathology , Encephalitis/enzymology , Encephalitis/etiology , Glucuronidase/metabolism , Mice , Scrapie/enzymology , Semliki forest virus , Sheep , Spinal Cord/pathology , Virus Diseases/enzymology , Virus Diseases/etiologySubject(s)
Arbovirus Infections/enzymology , Brain/enzymology , Encephalitis/enzymology , Lysosomes/enzymology , Acid Phosphatase/analysis , Animals , Arylsulfatases/analysis , Chikungunya virus , Encephalitis/pathology , Encephalitis Viruses, Tick-Borne , Female , Glucuronidase/analysis , Hexosaminidases/analysis , Mice , Peptide Hydrolases/analysis , Semliki forest virus , Sindbis Virus , Virus ReplicationABSTRACT
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.
Subject(s)
Arbovirus Infections/complications , Brain/radiation effects , Demyelinating Diseases/etiology , Animals , Antibody Formation/radiation effects , Arbovirus Infections/immunology , Brain/pathology , Demyelinating Diseases/immunology , Demyelinating Diseases/pathology , Female , Immunosuppression Therapy , Male , Mice , Semliki forest virusABSTRACT
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.