Pathogenesis of Central Nervous System Lesions in Visna Cell‐mediated Immunity and Lymphocyte Subsets in Blood, Brain, and Cerebrospinal Fluid

Torsteinsdóttir, Sigurbjörg; Georgsson, Guðmundur; Gísladóttir, E.; Rafnar, Björg; Pálsson, Páll A.; Pétursson, Gudmundur

doi:10.1111/j.1749-6632.1994.tb38905.x

Cited by 11 publications

(12 citation statements)

References 2 publications

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“…Expression of MHC was detected on cultured ovine microglial cells, with MHC-class I staining more prominent than MHC-class II staining. This is consistent with previous in vivo studies in which ovine parenchymal microglial cells were shown to express both MHCclass I and class II molecules (Torsteinsdottir et al, 1994;Bergsteinsdottir et al, 1998).…”

Section: Discussionsupporting

confidence: 82%

“…A common feature of the CNS pathology which can be reproduced by intracerebral inoculation of MVV is extensive perivascular cuf®ng and lymphocytic in®ltration of the neuroparenchyma. Although no correlation has been established between the extent of the in¯ammatory response in the CNS and the degree of clinical disease, early CNS disease is believed to be immune mediated Torsteinsdottir et al, 1992;1994). MVV infection of the CNS results in lesions of demyelination similar to those observed in multiple sclerosis in humans (Palsson, 1974).…”

Section: Introductionmentioning

confidence: 99%

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Phenotypic characterisation and infection of ovine microglial cells with Maedi-Visna Virus

Ebrahimi¹,

Allsopp²,

Fazakerley³

et al. 2000

J Neurovirol

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Maedi-Visna Virus (MVV) infection of the central nervous system (CNS) results in pathological changes, the mechanisms of which are poorly understood. MVV preferentially infects cell of the monocyte/macrophage lineage in vivo. The neuroparenchymal microglial cells are the resident tissue macrophages in the CNS and therefore likely targets for MVV infection. However, no information is currently available on the susceptibility of these cells to MVV infection or their contribution to neuropathological changes as a result of MVV infection. Highly enriched primary ovine microglial cell cultures were set up from brain tissues of lambs. These cells were amoeboid or bipolar with spikes, a morphology consistent with microglial cells of other species, and stained positive for CD1, CD11a, CD11c, CD14, MHC-class I, MHC-class II, and b-N-acetyl galactose, but not with markers of astrocytes or oligodendrocytes. These sheep microglial cells were permissive for MVV infection. Productive MVV infection resulted in selective transcriptional upregulation of the pro-in¯ammatory cytokines TNFa and IL-6. In contrast, there was no change in levels of transcripts for TGFb1, IL-1b, GM-CSF, IL-10, or IL-12. These data provide the ®rst evidence that ovine microglial cells can support productive infection with MVV, and that this leads to a selective upregulation of proin¯ammatory cytokines. These may contribute to visna neuropathology. Journal of NeuroVirology (2000) 6, 320 ± 328.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Phenotypic characterisation and infection of ovine microglial cells with Maedi-Visna Virus

Ebrahimi¹,

Allsopp²,

Fazakerley³

et al. 2000

J Neurovirol

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“…Similar ®ndings have been reported in Icelandic sheep infected with visna virus (Georgsson, 1994;Torsteinsdo Â ttir et al, 1992). These ®ndings are in contrast to HIV and SIV encephalitis in which there is limited in®ltration of lymphocytes (Budka, 1991).…”

Section: Discussionmentioning

confidence: 49%

Pathogenesis of ovine lentiviral encephalitis: Derivation of a neurovirulent strain by in vivo passage

Craig¹,

Sheffer²,

Meyer³

et al. 1997

J Neurovirol

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The lentiviruses of sheep replicate almost exclusively in macrophages and cause chronic interstitial pneumonia, arthritis, and mastitis, but only rarely encephalitis. This study was undertaken to determine whether a nonneurovirulent ®eld strain of ovine lentivirus isolated from joint¯uid that replicated productively in lung and joint macrophages could be adapted to enter and replicate in the brain and cause encephalitis. The ®eld isolate was passed seven times sequentially by intracerebral inoculation of sheep. The neuroadapted strain of virus caused severe encephalitis typical of visna in four of four sheep inoculated intracerebrally. The virus replicated to high titers in the brains of these animals and in cultured microglia. The in¯ammatory response in the brain was characterized by intense in®ltrates of macrophages and CD8 + and CD4 + T cells. Many of the perivascular macrophages demonstrated TNF-a expression and there was upregulation of MHC Class II antigen expression on both in¯ammatory cells and endothelium. Inoculation of this neuroadapted virus into the bone marrow of three animals resulted in persistent infection and cell-associated viremia, but not encephalitis. Virus was not detected in brains from these animals, indicating that the virus was not neuroinvasive. These data suggest that neuroinvasiveness and neurovirulence are separate pathogenic determinants, both of which are required for the development of encephalitis during natural infection.

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“…This is the first report to show which VISNA antigens were recognized by CD8 + CTL from VISNAinfected sheep. Cellular immune responses including CD8 + T-cell responses have been shown previously to develop after VISNA infection but little work has been carried out on antigen specificity (Bird et al, 1993;Blacklaws et al, 1994;Griffin et al, 1978;Larsen et al, 1982;Reyburn et al, 1992;Sihvonen, 1981;Torsteinsdó ttir et al, 1992). Fibroblasts from individual sheep were able to present different VISNA antigens to CTL, probably because of varying MHC class I backgrounds.…”

Section: Discussionmentioning

confidence: 99%

Mapping and characterization of visna/maedi virus cytotoxic T-lymphocyte epitopes

Barbezange

McConnell

et al. 2008

Journal of General Virology

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CD8 + cytotoxic T-lymphocyte (CTL) responses have been shown to be important in the control of human and simian immunodeficiency virus infections. Infection of sheep with visna/maedi virus (VISNA), a related lentivirus, induces specific CD8 + CTL in vivo, but the specific viral proteins recognized are not known. To determine which VISNA antigens were recognized by sheep CTL, we used recombinant vaccinia viruses expressing the different genes of VISNA: in six sheep (Finnish Landrace¾Dorset crosses, Friesland and Lleyn breeds) all VISNA proteins were recognized except TAT. Two sheep, shown to share major histocompatibility complex (MHC) class I alleles, recognized POL and were used to map the epitope. The pol gene is 3267 bp long encoding 1088 aa. By using recombinant vaccinia viruses a central portion (nt 1609-2176, aa 537-725) was found to contain the CTL epitope and this was mapped with synthetic peptides to a 25 aa region (aa 612-636). When smaller peptides were used, a cluster of epitopes was detected: at least three epitopes were present, at positions 612-623: DSRYAFEFMIRN; 620-631: MIRNWDEEVIKN; and 625-635: EEVIKNPIQAR. A DNA-prime-modified vaccinia virus Ankara (MVA)-boost strategy was employed to immunize four sheep shown to share MHC class I allele(s) with the sheep above. Specific CTL activity developed in all the immunized sheep within 3 weeks of the final MVA boost although half the sheep showed evidence of specific reactivity after the DNA-prime immunizations. This is the first report, to our knowledge, of induction of CTL by a DNA-prime-boost method in VISNA infection. INTRODUCTIONVisna/maedi virus (VISNA) establishes a life-long infection of sheep, leading to progressive inflammatory disease in multiple organs, e.g. interstitial pneumonitis, meningoencephalomyelitis, mastitis and arthritis (Narayan & Clements, 1989). VISNA is a member of the subfamily Lentivirinae, which includes human, simian, feline and bovine immunodeficiency viruses (HIV, SIV, FIV and BIV, respectively), equine infectious anaemia virus (EIAV) and the closely related caprine arthritis encephalitis virus (CAEV). Unlike HIV and other immunodeficiency viruses, VISNA infects cells of the monocyte/macrophage lineage and dendritic cells but not T lymphocytes (Gendelman et al., 1985(Gendelman et al., , 1986Gorrell et al., 1992;Ryan et al., 2000). Due to the tropism for mononuclear phagocytes, lymphoid tissues are considered to be important targets for the replication of VISNA (Blacklaws et al., 1995a; Pétursson et al., 1991). This restriction in tropism makes VISNA a unique model for understanding immunity to and pathogenesis of lentiviruses in the absence of T-cell infection in the infected host.Cytotoxic T-lymphocytes (CTL) play an important role in immune control of both acute and chronic viral infections and are key immunological mediators of viral clearance (Harty et al., 2000;Wong & Pamer, 2003). In lentiviral infections, control of replication of HIV and SIV has been linked strongly to robust specific CD8 + CTL although CD4 +...

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Pathogenesis of Central Nervous System Lesions in Visna Cell‐mediated Immunity and Lymphocyte Subsets in Blood, Brain, and Cerebrospinal Fluid

Cited by 11 publications

References 2 publications

Phenotypic characterisation and infection of ovine microglial cells with Maedi-Visna Virus

Phenotypic characterisation and infection of ovine microglial cells with Maedi-Visna Virus

Pathogenesis of ovine lentiviral encephalitis: Derivation of a neurovirulent strain by in vivo passage

Mapping and characterization of visna/maedi virus cytotoxic T-lymphocyte epitopes

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