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Biomedical subjects

O Narayan

Publications and source records attributed to O Narayan.

At least 181 records · Page 10Linked to original sources
PubMed1984

Slow virus-macrophage interactions. Characterization of a transformed cell line of sheep alveolar macrophages that express a marker for susceptibility to ovine-caprine lentivirus infections.

Visna-maedi of sheep and arthritis encephalitis of goats are slowly progressive diseases caused by serologically related lentiviruses. Lesions are inflammatory and can occur at one or many sites including the central nervous system, lungs, joints, and mammary glands. The viruses replicate in macrophages, and in the animal large numbers of infected macrophages can be obtained from inflamed tissues. To study virus-macrophage interactions we transformed sheep alveolar macrophages, which are natural virus target cells, with simian virus 40 and produced a macrophage cell line. The transformed cells grew into density-dependent monolayers and were subcultured after trypsin dissociation. They maintained histochemical and physiologic properties of macrophages as well as the ability to support replication of the lentiviruses. Rabbit antisera to these cells reacted with blood monocytes and only selected populations of tissue macrophages, including those in lung, synovium, mammary gland, and spleen. Microglia, Kupffer cells, and connective tissue histiocytes were not recognized by the sera. Since the tissues in which virus localizes in infected animals are the same as those recognized by the sera, the antimacrophage serum may provide an immunologic marker for virus-susceptible macrophages in the animal.

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PubMed1983

Selection of a fixative for identifying T cell subsets, B cells, and macrophages in paraffin-embedded mouse spleen.

Fixation techniques were investigated for their ability to preserve morphology, esterase activity and cell surface antigens in paraffin-embedded mouse lymphoid tissue. The avidin-biotin-peroxidase system was used to stain antigens Thy-1.2, Lyt-1, Lyt-2, RA32C2 and F4/80. Conventional fixatives were compared with fixatives containing periodate and lysine plus paraformaldehyde and/or glutaraldehyde. Conventional fixatives preserved esterase activity but not many cell surface antigens. Periodate-lysine fixatives allowed better preservation of membrane antigens, but esterase activity was often lost at antigen-preserving concentrations of paraformaldehyde or glutaraldehyde. However, a periodate-lysine fixative containing both paraformaldehyde and glutaraldehyde preserved esterase and showed good to excellent staining of Lyt-1, Thy-1.2, RA32C2, and F4/80. Lyt-2 could not be stained with any fixative, but was well preserved in frozen material post-fixed with periodate-lysine based fixatives. We conclude that with proper fixation immune cell surface markers can be identified in paraffin-embedded tissue.

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PubMed1983

Behavioral disease in rats caused by immunopathological responses to persistent borna virus in the brain.

Borna virus replicated persistently in the brains of rats, causing frenzied and apathetic behavioral states in sequence but no mortality. The transient frenzied behavior was caused by an immune-mediated, cytolytic, encephalitic response that was unexpectedly self-limiting. Cessation of active pathological processes coincided with the onset of the passive phase of the disease. This study thus demonstrates suppression of virus-specific inflammation despite continuous viral replication and describes a new mechanism by which chronic encephalitis may become established.

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PubMed1983

Pathogenesis of Borna disease in rats: immune-mediated viral ophthalmoencephalopathy causing blindness and behavioral abnormalities.

Borna disease virus is an unclassified agent that causes a rare but fatal encephalitis in horses in Germany. In experimental animals the virus causes acute fatal encephalitis in some instances and chronic encephalitis with abnormal behavior in others. In initial studies of the pathogenesis of the latter disease in rats, the virus was shown to replicate only in the nervous system, with the greatest concentration of infectivity in the cerebrum and eyes. Viral replication continued indefinitely in both newborn and adult rats. The adult animals developed self-limiting, necrotizing encephalitis in the cerebrum, with inflammation spreading to the retina. Inflammation receded after two months, however, with concomitant cessation of necrosis; static hydrocephalus was observed at this point. Levels of viral replication were unaffected by these changes. Rats became frenzied and aggressive during the encephalitic period but became permanently passive and inactive after inflammation receded. Infected neonates and immunosuppressed adults did not become ill. The frenzied behavior and subsequent blindness in immunocompetent adults were therefore attributed to a uniquely transient immunopathologic reaction targeted to centers in the limbic system and retinal neurons.

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PubMed1983

Activation of caprine arthritis-encephalitis virus expression during maturation of monocytes to macrophages.

Lentiviruses, which cause arthritis-encephalitis and maedi-visna in goats and sheep, respectively, cause persistent infections in these animals. The viruses replicate productively at low levels in macrophages in diseased organs such as the "maedi lung" and nonproductively in other cell types such as leukocytes in peripheral blood. Nonproductive infections become productive during in vitro cultivation of the cells. This study showed that monocytes were the only cells in the peripheral blood leukocytes of an infected animal in which virus was detected and that virus activation occurred only when these cells matured into macrophages. Only a minute fraction of cultured monocytes matured into macrophages, and viral infectivity was associated exclusively with this fraction. Antiglobulin-coated glass wool fragments were lethal for monocyte macrophages because of toxic phagocytosis, but had no effect on B or T lymphocytes. The simultaneous addition of the glass fragments and leukocytes to culture dishes resulted in no macrophage maturation and no virus production. The addition of the fragments to virus-producing macrophages caused the death of the cells and a decline in virus production. Virus production in less avidly phagocytic cells was unaffected by the glass. Thus, although macrophages may be permissive for virus replication, one mechanism for restricted virus expression in vivo may be physiological factors controlling the maturation of these cells.

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PubMed1983

Immunosuppression in goats inoculated with parainfluenza type 3 virus.

The humoral and cellular immune responses of goats experimentally infected with an ovine isolate of parainfluenza type 3 virus (PI-3) were examined. Virus neutralization and enzyme-linked immunosorbent assays were used to determine antibody in the serum and CSF. Lymphocyte stimulation, measured by [3H]thymidine incorporation into peripheral blood leukocytes, was used to determine cellular responses to phytomitogens and virus. There were significant suppression of peripheral blood leukocyte responses to T-cell mitogens early in the course of infection and delayed onset of virus-specific cell-mediated immunity. Delay in antibody formation did not occur. The suppression of mitogen response has been reported with other paramyxovirus infections. The importance of the suppressed cellular immune response for potentiating other infective agents is discussed.

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PubMed1983

Pathogenesis of neurovirulent influenza A virus infection in mice. Route of entry of virus into brain determines infection of different populations of cells.

Coinfection of a cell culture with a human and avian influenza A virus had yielded a recombinant virus with high neurovirulence for mice. This study reports on the comparative pathogenesis of central nervous system infection in mice between the parental human and the recombinant virus using the immunohistologic peroxidase-antiperoxidase method and virus assay of tissue suspensions. The human virus replicated poorly in mice and did not replicate in the brain even after intracerebral inoculation. In contrast, the recombinant virus replicated to high titer in the lung and brain with resulting viremia after inoculation of young mice by the intracerebral, intraperitoneal, or intranasal routes. Different populations of cells in the brain became infected after inoculation by each of the three routes: choroid plexus, and ependymal and subependymal cells after intracerebral inoculation; cells in perivenous areas, neurons in the olfactory bulbs and trigeminal ganglia and nuclear groups in the brainstem and midbrain after intranasal inoculation. Intraperitoneal inoculation resulted almost exclusively in the perivenous spread of the virus. The intranasal inoculation suggested that virus entry into the brain both by spread along nerve cell processes from the nasal mucosa to the brain and trigeminal ganglia and subsequent perivenous spread after viremia developed following virus replication in the lung. To dissect these two mechanisms we inoculated neonatal mice that had acquired high levels of serum antibody by nursing from actively immunized mothers. Intraperitoneal inoculation of these mice failed to cause infection, whereas intranasal inoculation resulted in the same pattern of cellular spread through the olfactory and trigeminal pathways as noted previously. This proved that this recombinant influenza virus could invade the central nervous system after infection via a natural route of infection. This highly neuroinvasive agent provides one example of the extent of virulence which can be acquired by recombination of apathogenic influenza viruses and raises a note of caution for adequate control of those agents generated in the laboratory.

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PubMed1982

Hematogenous origin of the inflammatory response in acute poliomyelitis.

To determine the origin of the inflammatory response, and in particular the microglial rod cell response, in acute viral encephalitis, 4-week-old Swiss mice were injected with tritiated thymidine to label actively dividing cells prior to infection with the Lansing type 2 strain of poliovirus. As expected, the majority of polymorphonuclear and mononuclear leukocytes within the central nervous system perivascular infiltrates were shown to be hematogenous in origin. As early as 24 hours after infection, isotope-labeled cells having light histological and ultrastructural features consistent with microglia and microglial rod cells were identified within brain parenchyma and were shown to participate in neuronophagia and formation of glial nodules. Supraependymal and suprachoroidal cells were also shown to contain the label. However, neither endothelial cells nor pericytes contained label as determined by electron microscopy. These studies support a hematogenous origin for all cellular elements of the classic inflammatory response in viral infections of brain.

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PubMed1982

Slow virus replication: the role of macrophages in the persistence and expression of visna viruses of sheep and goats.

Lentiviruses of sheep and goats cause slowly progressive diseases of the central nervous system (visna), lungs (maedi) and joints (arthritis) in their natural hosts. However, the virus target cell(s) in these diseases are still unknown. In this report, using laboratory-adapted Icelandic visna virus and several field strains recently obtained from sheep and goats with natural disease in the U.S.A., we show that macrophages became persistently infected when inoculated in culture. Furthermore, macrophages were an invariable source of virus from experimentally and naturally infected animals. Virus-producing macrophages developed minimal cytopathic changes and virus assembly occurred mainly intracellularly, accumulating in cytoplasmic vacuoles. In contrast to macrophages, sheep choroid plexus fibroblasts developed syncytial cytopathic changes after inoculation and virus maturation occurred at the cell surfaces. Replication of the Icelandic virus was highly productive in this system but that of the field viruses was very inefficient. In some cases these agents failed to replicate in the fibroblasts and no cytopathic effect occurred. This block in the field virus replication was, however, overcome when infected nonproducer fibroblasts were co-cultivated with macrophages. In these cases, virus production with attendant cytopathic effect in the fibroblasts required the continuous presence of macrophages because the cells reverted to a non-productive state when separated from macrophages and became productive again when subcultures were added to new macrophages. The roles of the macrophage as a virus target cell and virus inducer in the virus-macrophage-fibroblast interactions are discussed with inferences to the well-known phenomenon of restricted virus replication in infected animals and the immunopathological aspects of the diseases.

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PubMed1981

Pathogenesis of contagious streptococcal lymphadenitis in cats.

Transmission and pathogenesis studies were undertaken in cats inoculated orally with Lancefield group G beta-hemolytic streptococci. These bacteria, which had been isolated from cats during a natural episode of lymphadenitis, rapidly colonized the tonsils of inoculated cats and disseminated along lymphatic channels. Acute purulent inflammation of lymph nodes on the head and neck was followed by toxemia, which coincided with pyrexia and other signs of clinical illness.

Animals↗
PubMed1981

Neutralizing antibody spectrum determines the antigenic profiles of emerging mutants of visna virus.

The visna viruses are antigenically related nononcogenic retroviruses of sheep. The original strain was isolated from the brain of a paralyzed sheep in Iceland during the 1940s. The prototype strains has been passed serially in sheep and has undergone progressive antigenic change. Previous reports have shown that such antigenic changes in visna virus can be reproduced in infected cell cultures treated with neutralizing antibody. We now show that the antigenic profiles of the emerging mutants directly reflect the nature of the selecting antibody. Mutants with minor antigenic changes were selected by "early" sera which had a limited neutralization range. Mutants with greater antigenic changes were selected by "late" sera with a wide neutralization range. Mutants selected by early sera emerged rapidly and consistently in cultures, and these were antigenically very similar to one another. Mutants rarely emerged in cultures treated with late sera, but these viruses showed major antigenic changes. The data suggest that the evolution of antigenic mutants of visna virus progresses by a series of minor mutations which accumulate under the selective pressure of antibody.

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PubMed1981

Ovine progressive pneumonia: pathologic and virologic studies on the naturally occurring disease.

Pathologic and virologic studies were conducted on 13 mature ewes with serum precipitin antibodies to progressive pneumonia virus (PPV). Pulmonary lesions of ovine progressive pneumonia were found in 4 sheep, a meningoencephalitis resembling visna in 1 sheep, chronic proliferative carpal arthritis in 2, and massive lymphoid proliferation in the mammary gland in 3. Virus producing cytopathic effect typical of PPV was isolated from the lungs, mediastinal lymph node, spleen, and choroid plexus of 4 sheep and from the carpal synovium of 2 sheep with chronic carpal arthritis. Three viral isolates selected for further study were antigenically related to visna virus by immunofluorescence and immunodiffusion, but these 3 isolates were not neutralized by antisera to reference strains of visna virus. Seemingly, infection of sheep by ovine retroviruses is common in the United States, and these viruses are capable of causing disease in more than 1 organ system.

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PubMed1980

Contagious streptococcal lymphadenitis in cats.

A Lancefield group G beta-hemolytic streptococcus was isolated from a group of laboratory cats with acute lymphadenitis of the head and neck and systemic signs of sepsis. The infection appeared to be transmitted by the oral route and was experimentally reproduced in cats after the isolant was inoculated by oral and subcutaneous routes.

Animals↗
PubMed1980

Genomic changes associated with antigenic variation of visna virus durig persistent infection.

Visna virus undergoes antigenic change during persistent infection of sheep. Antigenic variants of visna virus were compared by using the genomic RNA and analyzing the large RNase T1-resistant oligonucleotides. Mutants isolated from a persistently infected sheep contained a small number of changes in their oligonucleotide patterns when compared with parental virus. To determine whether the changes in the nucleotide structure were clustered in one region of the genome, we determined the order of the oligonucleotides of the parental and mutant RNAs along the genome with respect to the 3' polyadenylylated end. All but one difference between the parental strain and the antigenic mutant used for mapping were located within 2 kilobases from the 3' terminus. Nucleotide sequence analyses showed that several of the oligonucleotides that differed in the parental and mutant RNAs could be accounted for by single base changes.

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