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Apport des modeles animaux dans la comprehension de l'encephalopathie SIDA

Apport des modeles animaux dans la comprehension de l'encephalopathie SIDA
Apport des modeles animaux dans la comprehension de l'encephalopathie SIDA

The neuropathology associated with HIV (Human Immunodeficiency Virus) infection is one of the major complications of this disease. The virological and cellular mechanisms by which HIV infection induces motor and cognitive disorders remain unknown. This lack of understanding of the pathophysiology is partly due to the difficulty of experimental analysis in man because only post-mortem samples from terminal phases of the disease and cerebrospinal fluid samples are available. Two animal models, very closely resembling human HIV infection, are available: the cat model infected FIV (Feline by Immunodeficiency Virus) and the macaque model infected by the SIVmac (Simian Immunodeficiency Virus) which have enabled us to conduct a longitudinal study of encephalopathy during primo-infection and the asymptomatic and pre-AIDS (Acquired Immune Deficiency Syndrome) phases. In the cat-FIV model, which presents the advantage of being non- infectious to man, and therefore easter to manipulate, it was shown that infected cats develop behavioural abnormalities and a neuropathology which resemble HIV dementia. Central nervous system lesions-induced by FIV are similar to those of HIV infection apart from the absence of multinucleated giant cells. This model was used to analyse the relationship between CNS lesions and the viral load of the brain and showed that the severity of the lesions contrasted with a low viral load. The pathophysiology of SIVmac infection in the rhesus macaque is almost identical to human infection with a more rapid course, since the duration of the asymptomatic phase is 6 months to 5 years, depending on the animal. We studied the relationship between lesions, viral load and cytokine production (IL-1β, IL-2, IL-6, TNFα, INFγ, TGF-β1) within the CNS. Our results show early, low-grade and constant infection of the brain. The dissociation between the viral load and the lesions observed is our favour of an indirect mechanism for the pathogenesis of these lesions. The relationship between lesions and the cytokine profile studied shows the importance of glial cells in the pathogenesis of the lesions.

Central nervous system, FIV, HIV, SIV
0395-501X
75-85
Boche, D.
bdcca10e-6302-4dd0-919f-67218f7e0d61
Gray, F.
863ce1c9-7cfa-49be-88c1-5534bf45991e
Khatissian, E.
616c1ecd-d182-435a-a315-05c8e9faf22d
Hurtrel, M.
9641f3f9-ddbf-44dc-9300-07689bbefc6c
Montagnier, L.
80c2ecb7-a62e-4b81-a1dd-5438bc61f05f
Hurtrel, B.
6798d5fc-3ad6-431f-89d7-f269f9a17c4f
Boche, D.
bdcca10e-6302-4dd0-919f-67218f7e0d61
Gray, F.
863ce1c9-7cfa-49be-88c1-5534bf45991e
Khatissian, E.
616c1ecd-d182-435a-a315-05c8e9faf22d
Hurtrel, M.
9641f3f9-ddbf-44dc-9300-07689bbefc6c
Montagnier, L.
80c2ecb7-a62e-4b81-a1dd-5438bc61f05f
Hurtrel, B.
6798d5fc-3ad6-431f-89d7-f269f9a17c4f

Boche, D., Gray, F., Khatissian, E., Hurtrel, M., Montagnier, L. and Hurtrel, B. (1997) Apport des modeles animaux dans la comprehension de l'encephalopathie SIDA. Archives d'Anatomie et de Cytologie Pathologiques, 45 (2-3), 75-85.

Record type: Article

Abstract

The neuropathology associated with HIV (Human Immunodeficiency Virus) infection is one of the major complications of this disease. The virological and cellular mechanisms by which HIV infection induces motor and cognitive disorders remain unknown. This lack of understanding of the pathophysiology is partly due to the difficulty of experimental analysis in man because only post-mortem samples from terminal phases of the disease and cerebrospinal fluid samples are available. Two animal models, very closely resembling human HIV infection, are available: the cat model infected FIV (Feline by Immunodeficiency Virus) and the macaque model infected by the SIVmac (Simian Immunodeficiency Virus) which have enabled us to conduct a longitudinal study of encephalopathy during primo-infection and the asymptomatic and pre-AIDS (Acquired Immune Deficiency Syndrome) phases. In the cat-FIV model, which presents the advantage of being non- infectious to man, and therefore easter to manipulate, it was shown that infected cats develop behavioural abnormalities and a neuropathology which resemble HIV dementia. Central nervous system lesions-induced by FIV are similar to those of HIV infection apart from the absence of multinucleated giant cells. This model was used to analyse the relationship between CNS lesions and the viral load of the brain and showed that the severity of the lesions contrasted with a low viral load. The pathophysiology of SIVmac infection in the rhesus macaque is almost identical to human infection with a more rapid course, since the duration of the asymptomatic phase is 6 months to 5 years, depending on the animal. We studied the relationship between lesions, viral load and cytokine production (IL-1β, IL-2, IL-6, TNFα, INFγ, TGF-β1) within the CNS. Our results show early, low-grade and constant infection of the brain. The dissociation between the viral load and the lesions observed is our favour of an indirect mechanism for the pathogenesis of these lesions. The relationship between lesions and the cytokine profile studied shows the importance of glial cells in the pathogenesis of the lesions.

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More information

Published date: 1 January 1997
Alternative titles: Contribution of animal models to the understanding of AIDS encephalopathy
Keywords: Central nervous system, FIV, HIV, SIV

Identifiers

Local EPrints ID: 438815
URI: http://eprints.soton.ac.uk/id/eprint/438815
ISSN: 0395-501X
PURE UUID: c2429da9-1e6b-48d1-aea2-cc3592a9f7bd
ORCID for D. Boche: ORCID iD orcid.org/0000-0002-5884-130X

Catalogue record

Date deposited: 24 Mar 2020 17:52
Last modified: 23 Jul 2022 01:47

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Contributors

Author: D. Boche ORCID iD
Author: F. Gray
Author: E. Khatissian
Author: M. Hurtrel
Author: L. Montagnier
Author: B. Hurtrel

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