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Experimental panencephalitis induced in suckling mice by parainfluenza I (6/94) virus. III. Ultrastructural studies.

Intracerebral inoculation of newborn mice with Parainfluenza I (6/94) virus produces a chronic panencephalitis. Electron microscopic studies were carried out over 125 days of the infection. Productive infection of choroidal and ependymal epithelial cells was seen from postinoculation days 2nd to the 8th. Fusion of adjacent choroid and ependymal cells resulted in giant cell formation. Completed virions were seen adsorbed to circulating macrophages and these cells replicated intracytoplasmic nucleocapsids. Neuronal infection was evident on the 3rd postinoculation day, was widespread by the 6th day postinoculation and persisted to the 35th day postinoculation. Nucleocapsid alignment and budding from neuronal plasma membranes was never seen. An initially intense mononuclear cell infiltrate subsided by the 35th day but residual inflammation persisted throughout the study. Late in the course of the infection, vacuolation of the neuropil and a periventricular and deep cerebral spongiform change was seen which could not be directly associated with local viral replication. These ultrastructural findings are correlated with prior light microscopic, virological and immunofluorescent studies of the infection and compared to other experimental models of myxovirus central nervous system infections.

Animals↗

Studies on persistent infections of tissue cultures. IV. Evidence for the production of an interferon in MCN cells by myxoviruses.

In previous reports of this series, it was shown that persistent infection of MCN cultures with certain myxoviruses rendered the cells insusceptible to superinfection by several cytopathogenic viruses. It was thought that production of an interferon might be the cause of this resistance and efforts to confirm this suggestion have been presented. Addition of ultraviolet-inactivated myxoviruses (mumps, Newcastle disease, influenza A, and Sendai) to MCN cultures for periods of 2 to 3 hours, followed by washing and refeeding of the cells, led to the subsequent release into the media of a substance which induced in fresh MCN cells a transitory resistance to infection by vesicular stomatitis virus, and prevented incomplete reproductive cycles of influenza A and Sendai viruses. Media containing this substance were free of detectable hemagglutinating activity and viral complement-fixing antigens. The substance was not neutralized by specific antiviral sera; it was not sedimentable by high speed centrifugation; it was not adsorbed onto red cells; but it was inactivated by trypsin. Thus, its properties matched those of the interferon described by Isaacs and his associates. A comparison of the extent of resistance induced in MCN cells by decreasing doses of ultraviolet-inactivated myxoviruses (interference test) and the protection afforded by the media removed from the cultures prior to challenge and transferred to fresh MCN tubes (interferon test) revealed that wherever interference became detectable in the cells, the media of the corresponding cultures contained some interferon. Interferon was obtained by inactivated myxoviruses also from primary cell cultures by the same techniques, but not from HeLa cells. Interferons derived from one type of culture may protect others equally well or show a certain degree of host specificity in that resistance in homologous cells may be somewhat more pronounced than in heterologous cultures. No resistance could be induced in HeLa cells by the interferon preparations employed. Interferon was detected also in MCN cultures, persistently infected with mumps virus. Its concentration was apparently too small in carrier cultures maintained as routine to be measurable. However, when the cells were grown in heavy sheets in roller bottles, and especially when the volume of medium was reduced for several days prior to harvest, interferon became readily detectable. These results strengthen the suggestion that interferon may play a decisive role in the establishment and maintenance of persistent infections in the system under study. Its nature, source, mode of action, and exact role in persistent infection remains to be elucidated.

Animals↗

Tropical pyomyositis in the Solomon Islands: clinical and aetiological features.

A prospective study of tropical pyomyositis (TP) in the Solomon Islands' Western Province followed 48 cases (mean age 10.6 years) from a population of 20,000 Melanesians over a two-year period. 32 patients were under 10 years and the male:female ratio was 1.7. Affected muscle was painful, swollen and often fluctuant but hard and indurated in presuppurative lesions. Abscesses, single in 40 and multiple in 8 subjects, were sited in the large muscles of the buttock, thigh, shoulder, arm and back on 52 occasions (90%). They contained 5-200 ml of pus which invariably grew penicillin-resistant Staphylococcus aureus sensitive to cloxacillin and erythromycin. All phage typable strains were identified as group 2 in contrast to the wider range of types found at carrier sites in otherwise healthy controls. TP was preceded by trauma in 30 cases (63%) and 26 (55%) of the patients had pre-existing pyoderma. Histological examination of clinically unaffected muscle biopsies from 10 subjects with solitary (7) or multiple (3) abscesses showed no abnormality. Serological evidence of previous infection with adenoviruses or myxoviruses was present in the same proportion (41-42%) of controls as of 22 patients tested. The results provide no evidence for antecedent diffuse myositis, viral or parasitic infections or nutritional deficiencies but support the role of trauma in localizing haematogenous skin staphylococci into damaged muscle.

Child↗

[Sudden death of a two-year-old boy with influenza A virus infection: study of an autopsy case].

UNLABELLED: Influenza A virus infections are common in childhood and infancy and are often underdiagnosed while serious or lethal forms are rare. CASE-REPORT: We describe a case of sudden death in a two-year-old boy. Pathologic findings at autopsy were consistent with Myxovirus influenzae A virus infection and the virus was isolated by post mortem PCR. CONCLUSION: In the case of sudden death in infants, especially if pathologic findings are compatible with a viral infection, PCR may allow identification of the causative virus.

Autopsy↗

[Correlation between structure and pathogenicity of myxoviruses (author's transl)].

Myxoviruses (ortho- and paramyxoviruses) possess on their surface two virus-specific glycoproteins, the functions of which are largely understood; These glycoproteins are synthesized on the rought endoplasmic reticulum, and during their transport to the plasma membrane on smooth intracellular membranes, they undergo modification through proteolytic cleavage. In this way, the orthomyxovirus hemagllutinin is converted from a high-molecular weight form (HA) into two smaller cleavage products (HA1 and HA2). With the paramyxoviruses, the glycoprotein F, which is responsible for fusion and hemolysis, is derived from proteolytic cleavage of a precursor, F0. Furthermore, with a few strains of avirulent NDV, a precursor of the hemagglutinin-neuraminidase complex, (HN0), has been identified which again, as a result of proteolysis, undergoes cleavage to HN. Whether cleavage takes place is as much dependent on the structure of the glycoprotein as on the host cell type. Proteolytic cleavage is indeed not necessary for virus particle production but is required for infectivity. Virus particles which possess the uncleaved glycoproteins may be activated by in vitro treatment with trypsin. As evidenced by experiments with orthomyxovirus recombinants, the glycoproteins alone do not determine the pathogenicity of the viruses. With paramyxoviruses, the pathogenic and apathogenic strains show clear differences in their host range spectrum which is directly related to the sensitivity of their glycoproteins twoard proteases. These observations provide an initial sketch for the molecular basis of infectivity and pathogenicity with myxoviruses.

Animals↗

Andes virus stimulates interferon-inducible MxA protein expression in endothelial cells.

MxA is a cellular protein activated in cells treated with type I interferons. MxA protein is a member of the dynamin superfamily of large guanosine triphosphatases. A unique property of Mx1 GTPases is their antiviral activity against a wide range of RNA viruses. Replication of several hantavirus strains is inhibited in cells constitutively expressing MxA protein. We have found that Andes virus (ANDV) infection up regulates transcription of MxA RNA and expression of MxA protein in human endothelial cells in vitro. Activation of MxA gene expression requires virus replication. Up-regulation of MxA gene expression in hantavirus infected cells varies depending on the cell type. The degree of activation of MxA gene expression is inversely correlated with the efficiency of hantavirus replication. Additionally, MxA protein is co-localized with hantavirus nucleocapsid protein in infected cell. Our data suggest that MxA by interacting with the virus nucleocapsid protein inhibits production of new infectious virus particles.

Animals↗