Abstract
We examined the distribution in the perivascular spaces of Visna/maedi antigen, T cells (CD3+, CD4+ and CD8+), B cells and macrophages by immunohistochemistry in 22 natural cases of Visna/maedi encephalitis. Sheep showed lymphocytic or histiocytic lesions. In mild lymphocytic lesions, the viral antigen was detected in perivascular cuffs where CD8+ T cells predominated, but in severe lymphocytic lesions, sparse antigen was identified, and CD8+/CD4+ T cells appeared in a similar proportion in multilayer perivascular sleeves. In histiocytic lesions, vessels were surrounded by macrophages with abundant viral antigen, with CD8+/CD4+ T cells and B cells in the periphery. These results could reflect different stages of virus neuroinvasion and clarify the neuropathogenesis of Visna/maedi encephalitis.
References
Benavides J, Fuertes M, García-Pariente C, Ferreras MC, García Marín JF, Pérez V (2006a) Natural cases of Visna in sheep with myelitis as the sole lesion in the central nervous system. J Comp Pathol 134:219–230
Benavides J, Garcia-Pariente C, Fuertes M, Ferreras MC, Garcia-Marin JF, Juste RA, Perez V (2009) Maedi-Visna: the meningoencephalitis in naturally occurring cases. J Comp Pathol 140:1–11
Benavides J, García-Pariente C, Gelmetti D, Fuertes M, Ferreras MC, García-Marín JF, Pérez V (2006b) Effects of fixative type and fixation time on the detection of Maedi Visna virus by PCR and immunohistochemistry in paraffin-embedded ovine lung samples. J Virol Methods 137:317–324
Benavides J, Gomez N, Gelmetti D, Ferreras MC, Garcia-Pariente C, Fuertes M, Garcia-Marin JF, Perez V (2006c) Diagnosis of the nervous form of Maedi-Visna infection with a high frequency in sheep in Castilla y Leon, Spain. Vet Rec 158:230–235
Blacklaws BA (2012) Small ruminant lentiviruses: immunopathogenesis of visna-maedi and caprine arthritis and encephalitis virus. Comp Immunol Microbiol Infect Dis 35:259–269
Christodoulopoulos G (2006) Maedi-Visna: clinical review and short reference on the disease status in Mediterranean countries. Small Ruminant Res 62:47–53
Craig LE, Sheffer D, Meyer AL, Hauer D, Lechner F, Peterhans E, Adams RJ, Clements JE, Narayan O, Zink MC (1997) Pathogenesis of ovine lentiviral encephalitis: derivation of a neurovirulent strain by in vivo passage. J Neurovirol 3:417–427
Cutlip RC, Lehmkuhl HD, Schmerr MJ, Brogden KA (1988) Ovine progressive pneumonia (maedi-visna) in sheep. Vet Microbiol 17:237–250
Dawson M (1987) Pathogenesis of maedi-visna. Vet Rec 120:451–454
Ebrahimi B, Allsopp TE, Fazakerley JK, Harkiss GD (2000) Phenotypic characterisation and infection of ovine microglial cells with Maedi-Visna virus. J Neurovirol 6:320–328
Duval R, Bellet V, Delebassee S, Bosgiraud C (2002a) Implication of caspases during maedi-visna virus-induced apoptosis. J Gen Virol 83:3153–3161
Duval R, Delebassee S, Cardot PJ, Bosgiraud C (2002b) Visna virus-induced cytopathic effect in vitro is caused by apoptosis. Arch Virol 147:943–959
Esiri MM, Gay D (1990) Immunological and neuropathological significance of the Virchow-Robin space. J Neurol Sci 100:3–8
Freel SA, Saunders KO, Tomaras GD (2011) CD8(+) T-cell-mediated control of HIV-1 and SIV infection. Immunol Res 49:135–146
Gelmetti D, Gibelli L, Brocchi E, Cammarata G (2000) Using a panel of monoclonal antibodies to detect Maedi virus (MV) in chronic pulmonary distress of sheep. J Virol Methods 88:9–14
Georgsson G (1994) Neuropathologic aspects of lentiviral infections. Ann N Y Acad Sci 724:50–67
Georgsson G, Houwers DJ, Palsson PA, Petursson G (1989) 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. Acta Neuropathol 77:299–306
Georgsson G, Nathanson N, Palsson PA, Petursson G (1976) The pathology of visna and maedi in sheep. Front Biol 44:61–96
Gómez N, González J, Corpa JM, Pérez V, García Marín JF (1999) Diagnóstico de la forma nerviosa del maedi-visna en ovinos de aptitud lechera. Producción Ovina y Caprina 24:393–397
Kim WK, Corey S, Alvarez X, Williams K (2003) Monocyte/macrophage traffic in HIV and SIV encephalitis. J Leukoc Biol 74:650–656
Kim WK, Corey S, Chesney G, Knight H, Klumpp S, Wuthrich C, Letvin N, Koralnik I, Lackner A, Veasey R, Williams K (2004) Identification of T lymphocytes in simian immunodeficiency virus encephalitis: distribution of CD8+ T cells in association with central nervous system vessels and virus. J Neurovirol 10:315–325
Leginagoikoa I, Juste RA, Barandika J, Amorena B, De Andres D, Lujan L, Badiola J, Berriatua E (2006) Extensive rearing hinders Maedi-Visna Virus (MVV) infection in sheep. Vet Res 37:767–778
Lujan L, Garcia Marin JF, Fernandez de Luco D, Vargas A, Badiola JJ (1991) Pathological changes in the lungs and mammary glands of sheep and their relationship with maedi-visna infection. Vet Rec 129:51–54
Marcondes MC, Burudi EM, Huitron-Resendiz S, Sanchez-Alavez M, Watry D, Zandonatti M, Henriksen SJ, Fox HS (2001) Highly activated CD8(+) T cells in the brain correlate with early central nervous system dysfunction in simian immunodeficiency virus infection. J Immunol 167:5429–5438
Panitch H, Petursson G, Georgsson G, Palsson PA, Nathanson N (1976) Pathogenesis of visna. III. Immune responses to central nervous system antigens in experimental allergic encephalomyelitis and visna. Lab Invest 35:452–460
Peluso R, Haase A, Stowring L, Edwards M, Ventura P (1985) A Trojan horse mechanism for the spread of visna virus in monocytes. Virology 147:231–236
Persidsky Y (1999) Model systems for studies of leukocyte migration across the blood–brain barrier. J Neurovirol 5:579–590
Polledo L, Gonzalez J, Benavides J, Morales S, Martinez-Fernandez B, Delgado L, Reina R, Glaria I, Perez V, Ferreras MC, Garcia Marin JF (2011) Patterns of lesion and local host cellular immune response in natural cases of ovine maedi-visna. J Comp Pathol 147:1–10
Schmitz JE, Kuroda MJ, Santra S, Sasseville VG, Simon MA, Lifton MA, Racz P, Tenner-Racz K, Dalesandro M, Scallon BJ, Ghrayeb J, Forman MA, Montefiori DC, Rieber EP, Letvin NL, Reimann KA (1999) Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283:857–860
Sigurdsson B, Palsson P, Grimsson H (1957) Visna, a demyelinating transmissible disease of sheep. J Neuropathol Exp Neurol 16:389–403
Strazza M, Pirrone V, Wigdahl B, Nonnemacher MR (2011) Breaking down the barrier: the effects of HIV-1 on the blood–brain barrier. Brain Research 1399:96–115
Thormar H (2005) Maedi-visna virus and its relationship to human immunodeficiency virus. AIDS Rev 7:233–245
Torsteinsdottir S, Andresdottir V, Arnarson H, Petursson G (2007) Immune response to maedi-visna virus. Front Biosci 12:1532–1543
Torsteinsdottir S, Georgsson G, Gisladottir E, Rafnar B, Palsson PA, Petursson G (1992) Pathogenesis of central nervous system lesions in visna: cell-mediated immunity and lymphocyte subsets in blood, brain and cerebrospinal fluid. J Neuroimmunol 41:149–158
Williams K, Alvarez X, Lackner AA (2001a) Central nervous system perivascular cells are immunoregulatory cells that connect the CNS with the peripheral immune system. Glia 36:156–164
Williams KC, Corey S, Westmoreland SV, Pauley D, Knight H, deBakker C, Alvarez X, Lackner AA (2001b) Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques: implications for the neuropathogenesis of AIDS. J Exp Med 193:905–915
Acknowledgments
This work was supported by grants from the Spanish Ministry of Education (AGL2007-66874-CO4-04/GAN) and from the Junta of Castilla y León (LE36A12-1). L. Polledo holds a grant from the Ministry of Education (AP2007-02007). We thank the veterinarians for providing cases and Gloria Belver for technical assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Polledo, L., González, J., Benavides, J. et al. Perivascular inflammatory cells in ovine Visna/maedi encephalitis and their possible role in virus infection and lesion progression. J. Neurovirol. 18, 532–537 (2012). https://doi.org/10.1007/s13365-012-0131-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13365-012-0131-0