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Biomedical subjects

G Pétursson

Publications and source records attributed to G Pétursson.

At least 19 recordsLinked to original sources
PubMed2003

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.

Administration, Intranasal↗
PubMed1998

Biological and genetic differences between lung- and brain-derived isolates of maedi-visna virus.

During the epidemic caused by maedi-visna virus (MVV) of sheep in Iceland, the pulmonary affection, maedi, was the predominant clinical manifestation. In some flocks, however, a central nervous system (CNS) affection, visna, was the main cause of morbidity and mortality. As there is only one breed of sheep in the country, host factors did apparently not play an important role in the different clinical manifestations. To obtain some information on possible viral genetic determinants of neurotropism and neurovirulence we studied both phenotypic and genotypic properties of two maedi-visna virus strains; a strain that was originally isolated from the brain of sheep with encephalitis (visna), and another strain isolated from the lungs of a sheep suffering from pneumonia (maedi). The brain isolate was found to grow faster in sheep choroid plexus cells than the lung isolate, whereas the growth rate in macrophages was similar for the maedi and visna virus strains. Intracerebral inoculation indicated that the visna virus isolate induced more severe brain lesions than the maedi isolate. In addition, a pathogenic molecular clone derived from a visna strain (KV1772kv72/67) was tested for growth in sheep choroid plexus cells and macrophages. The molecularly cloned virus retained the fast growth rate in choroid plexus cells. The nucleotide sequence of the env gene and the U3 of the LTR was determined for the maedi strain and compared to that of the visna strains. There was an 11.7% difference in deduced amino acid sequence in the Env protein and a 6% difference in the LTR. The molecular clone KV1772kv72/67 will be a useful reagent for characterization of viral determinants of cell tropism in vitro and possibly neurovirulence in vivo.

Amino Acid Sequence↗
PubMed1998

Visna virus dUTPase is dispensable for neuropathogenicity.

The major part of the dUTPase-encoding region of the visna virus genome was deleted. Intracerebral injection of the mutant virus resulted in a somewhat reduced viral load compared to that resulting from injection of the wild type, especially in the lungs, but the neuropathogenic effects were comparable. The dUTPase gene is dispensable for induction of lesions in the brain.

Animals↗
PubMed1997

In vivo and in vitro infection with two different molecular clones of visna virus.

The behavior of two genetically different molecular clones of visna virus KV1772-kv72/67 and LV1-1KS1 was compared in vivo and in vitro. On intracerebral inoculation, clone KV1772-kv72/67 induced a similar response in five sheep as has already been reported with neurovirulent derivates of visna virus. Virus was frequently isolated from blood, cerebrospinal fluid (CSF), and lymphoid organs and induced characteristic central nervous system (CNS) lesions. A strong humoral immune response was detected by ELISA, immunoblotting, and neutralization. Six sheep infected with clone LV1-1KS1 showed a completely different picture. No virus could be isolated from blood or CSF during 6 months of infection. At sacrifice all organs were virus-negative except the CNS of one sheep. None of the six sheep developed significant neutralizing antibodies and only low titer antibodies were detected by ELISA and immunoblotting. Minimal CNS lesions were present in one sheep. The molecular clones were also tested in sheep choroid plexus cells (SCP) and macrophages. In macrophages LV1-1KS1 replicated to a significantly lower titer but induced much more cell fusion than KV1772-kv72/67. The clones replicated equally well in SCP cells. Thus, these molecular clones of visna virus, which differ only by 1% in nucleotide sequence, showed a profound difference in replication and pathogenicity both in vitro and in vivo. These results can be used to map viral genetic determinants important for host-lentivirus interactions.

Animals↗
PubMed1996

Replication properties of dUTPase-deficient mutants of caprine and ovine lentiviruses.

The virion-associated dUTPase activities of caprine arthritis-encephalitis virus (CAEV) and visna virus were determined by using an assay which measure the actual ability of the dUTPase to prevent the dUTP misincorporations into cDNA during reverse transcription. We showed that the CAEV molecular clone from the Cork isolate was dUTPase defective as a result of a single amino acid substitution. Using this point mutant and deletion mutants of CAEV as well as a deletion mutant of visna virus, we demonstrated that dUTPase-deficient viruses replicate similarly to wild-type viruses in dividing cells but show delayed replication in nondividing primary macrophages.

Animals↗
PubMed1994

Pathogenesis of central nervous system lesions in visna cell-mediated immunity and lymphocyte subsets in blood, brain, and cerebrospinal fluid.

The time course and titers of antibodies did not correlate with the severity of CNS lesions whereas the CMI did, indicating that CMI may play an important role in lesion development. The correlation of the number of CD8 positive cells in the CSF with the severity of lesions and the reversed ratio of CD4/CD8 positive cells in the diffusely infiltrated neuroparenchyma indicates that the CD8 positive T cells may be an important effector cell in the induction of CNS lesions.

Animals↗
PubMed1992

Pathogenesis of central nervous system lesions in visna: cell-mediated immunity and lymphocyte subsets in blood, brain and cerebrospinal fluid.

There are several indications that central nervous system (CNS) lesions in visna are immune-mediated and that cell-mediated immunity (CMI) may be of importance in the initiation of the lesions. To study the role of CMI in the pathogenesis of CNS lesions, five sheep were infected by intracerebral inoculation with visna virus and observed for 1 year. The following parameters were monitored at regular intervals: (1) neutralizing and ELISA antibodies; (2) visna virus-specific stimulation of lymphocytes from peripheral blood; (3) lymphocyte subpopulations in peripheral blood, cerebrospinal fluid (CSF) and brain at sacrifice. The CNS lesions were graded and compared with other parameters. The time course and titers of antibodies did not correlate with the severity of CNS lesions whereas the CMI did, indicating that CMI may play an important role in lesion development. The correlation of the number of CD8-positive cells in the CSF with the severity of lesions and the reversed ratio of CD4/CD8-positive cells in the diffusely infiltrated neuroparenchyma indicates that the CD8-positive T lymphocyte may be an important effector cell in the induction of CNS lesions.

Animals↗
PubMed1991

Human and ovine lentiviral infections compared.

Maedi-visna virus (MVV) of sheep was the first lentivirus to be isolated. The genomic organization of MVV is very similar to that of human immunodeficiency virus (HIV) with several genes regulating the expression of the viral genome. Viral replication is severely restricted in the host and some cells apparently contain the genetic information in a DNA provirus form with little or no expression of viral antigens. This seems to be a major factor in causing the "slowness" of lentiviral infections and the persistence of the virus in the host since the immune system may not recognize the provirus-containing cells. The target cells for HIV and MVV are similar although T4 lymphocytes are not specifically destroyed in maedi-visna. There are also certain similarities in the pathological changes in both diseases, both in the central nervous system, the lungs and the lymphatic system. Although the severe final immunodeficiency state characteristic of AIDS has not been observed in maedi-visna, the basic biological features of the MVV and its interaction with host cells are so similar to HIV infection, that we consider ovine maedi-visna useful animal model for the human lentivirus infections.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Visna and AIDS--various comparative aspects].

Visna, a lingering meningo-encephalitis in sheep, was one of the diseases on which B. Sigurdsson based his theory of a special group of disorders called slow infections. The cause of the disease, a retrovirus, was isolated in 1957. Visna is now classified in a subgroup of retroviridae, lentivirinae, together with virus types in animals and the human immune deficiency virus HIV. Notwithstanding that Visna has been eradicated among Icelandic sheep for 25 years research into this virus continues since it bears many similarities to HIV and also MS.

Antigenic Variation↗
PubMed1989

Expression of viral antigens in the central nervous system of visna-infected sheep: an immunohistochemical study on experimental visna induced by virus strains of increased neurovirulence.

Icelandic sheep were infected by intracerebral inoculation with visna virus strains of increased neurovirulence. The character and severity of pathological lesions were studied in brains from four sheep that developed clinical signs 5 to 12 weeks after infection. Viral antigens were identified by immunostaining using mouse monoclonal antibodies against two core proteins and the Avidin-Biotin method of detection. The pathological lesions were in general more severe than observed following infection with the parent strain K1514. Primary demyelination, a late manifestation of infection with K1514, was detected. Thus, in addition to causing more severe pathological lesions, these neurovirulent strains apparently have an increased potential to induce primary demyelination. Viral antigens were detected in lymphocytes, plasma cells, macrophages, endothelial cells, pericytes, fibroblasts and choroidal epithelial cells. Neurons and glial cells were antigen negative. The spectrum of infected cells in the brain was similar to that observed in infections with human immunodeficiency virus. These results do not support the view that the demyelination is caused by immunological damage to infected oligodendrocytes. A perturbation of the function of oligodendrocytes through a non-productive infection could be the underlying pathogenetic mechanism and/or a non-specific demyelination due to the intense inflammatory reaction.

Animals↗
PubMed1989

Maedi-visna in sheep: host-virus interactions and utilization as a model.

Controlled animal experiments with the ovine maedi-visna virus, the prototype lentivirus, have been carried out for almost 40 years. This non-oncogenic virus leads to a life-long, persistent infection with slow development of lesions in the lungs and in the central nervous system. The virus is present in many cells in a DNA provirus state and its replication and expression is highly restricted in vivo. The basic biological features of maedi-visna virus are quite similar to those of HIV and this ovine lentiviral disease may be useful as a model for infection with human lentiviruses.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Immunohistochemical staining of cells in the brain of a patient with acquired immune deficiency syndrome (AIDS) with a monoclonal antibody to visna virus.

Several monoclonal antibodies to different epitopes of the two major core proteins of visna virus, p25 and p15, were tested with the Avidin-Biotin immunostaining method on formaldehyde-fixed and paraffin-embedded sections of brains from patients with acquired immune deficiency syndrome (AIDS) who had shown neurological symptoms at death. In one of five AIDS cases a few cells, mainly inflammatory cells, showed a positive staining with a monoclonal antibody to the p25 core protein of visna.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Antigenic drift in visna: virus variation during long-term infection of Icelandic sheep.

A group of 20 Icelandic sheep were infected intracerebrally with visna virus strain 1514, and 209 virus isolates were obtained from the blood, cerebrospinal fluid, and central nervous system (CNS) over a period of 7 years, during which eight animals developed clinical signs of visna necessitating sacrifice. (i) Using type-specific antisera, it was found that 12 (16%) of 76 isolates tested escaped neutralization. These 12 variant viruses were distributed randomly among animals and over time, and did not replace the infecting strain even though all sheep developed homotypic antibody within 3 months of infection. The one exception was sheep no. 1557 (an animal without clinical visna), where the last six isolates were variants. (ii) A total of 35 blood and CNS isolates from seven of these sheep (including five with clinical visna) were tested against serial samples of their own sera. Autologous antisera neutralized all isolates tested with the exception of isolates from sheep 1557. None of the isolates obtained at sacrifice from the five sheep with clinical visna escaped neutralization with autologous antisera. These data suggest that although variant viruses are encountered at considerable frequency during long-term infection of Icelandic sheep, the variants usually do not replace the infecting strain. Antigenic drift does not appear to be essential for virus persistence or for the development of clinically evident CNS lesions.

Animals↗