Article (Scientific journals)
Cell dynamics and immune response to BLV infection: a unifying model
Florins, Arnaud-Francois; Gillet, Nicolas; Asquith, Becca et al.
2007In Frontiers in Bioscience: A Journal and Virtual Library, 12, p. 1520-1531
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Keywords :
Apoptosis; BLV; Expression; HTLV; Homeostasis; Immune response; Leukemia; Therapy; Apoptose; Homéostasie; Réponse immunitaire; Leucémie; Thérapie
Abstract :
[en] Bovine Leukemia virus (BLV) is the natural etiological agent of a lymphoproliferative disease in cattle. BLV can also be transmitted experimentally to a related ruminant species, sheep, in which the pathogenesis is more acute. Although both susceptible species develop a strong anti-viral immune response, the virus persists indefinitely throughout life, apparently at a transcriptionally silent stage, at least in a proportion of infected cells. Soon after infection, these humoral and cytotoxic activities very efficiently abolish the viral replicative cycle, permitting only mitotic expansion of provirus-carrying cells. Short term cultures of these infected cells initially indicated that viral expression protects against spontaneous apoptosis, suggesting that leukemia is a process of accumulation of long-lived cells. This conclusion was recently reconsidered following in vivo dynamic studies based on perfusions of nucleoside (bromodeoxyuridine) or fluorescent protein markers (CFSE). In sheep, the turnover rate of infected cells is increased, suggesting that a permanent clearance process is exerted by the immune system. Lymphocyte trafficking from and to the secondary lymphoid organs is a key component in the maintenance of cell homeostasis. The net outcome of the immune selective pressure is that only cells in which the virus is transcriptionally silenced survive and accumulate, ultimately leading to lymphocytosis. Activation of viral and/or cellular expression in this silent reservoir with deacetylase inhibitors causes the collapse of the proviral loads. In other words, modulation of viral expression appears to be curative in lymphocytic sheep, an approach that might also be efficient in patients infected with the related Human T-lymphotropic virus type 1. In summary, a dynamic interplay between BLV and the host immune response modulates a complex equilibrium between (i) viral expression driving (or) favoring proliferation and (ii) viral silencing preventing apoptosis. As conclusion, we propose a hypothetical model unifying all these mechanisms.
Disciplines :
Animal production & animal husbandry
Biochemistry, biophysics & molecular biology
Author, co-author :
Florins, Arnaud-Francois ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech > Gembloux Agro-Bio Tech
Gillet, Nicolas ;  Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Asquith, Becca;  Imperial College, London > Department of Immunology
Boxus, Mathieu ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech > Gembloux Agro-Bio Tech
Burteaux, Catherine;  Université de Liège - ULiège > Gembloux Agro-Bio Tech
Twizere, Jean-Claude  ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech > Gembloux Agro-Bio Tech
Urbain, Patrice;  Université de Liège - ULiège > Gembloux Agro-Bio Tech
Vandermeers, Fabian ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech
Debacq, Christophe;  GlaxoSmithKline Biologicals, Belgium
Sanchez-alcaraz, Maria Teresa;  University of Toronto - U of T > Department of Medical Genetics and Microbiology
Schwartz-Cornil, Isabelle;  Institut Scientifique de Recherche Agronomique - INRA > U892
Kerkhofs, Pierre;  Veterinary and Agrochemical research centre, Belgium > Department of virology
Jean, Geneviève ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech > Gembloux Agro-Bio Tech
Thewis, André ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech > Gembloux Agro-Bio Tech
Hay, Jack;  University of Toronto - U of T > Department of Immunology
Mortreux, Franck;  Centre National de la Recherche Scientifique - CNRS > Unité d'Oncologie Virale - UMR 5537
Wattel, Eric;  Centre National de la Recherche Scientifique - CNRS > Unité d'Oncologie Virale - UMR 5537
Reichert, Michal;  Veterinary Research Institute, Poland
Burny, Arsène ;  Université de Liège - ULiège > Agro Biotech Gembloux
Kettmann, Richard ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech > Gembloux Agro-Bio Tech
Bangham, Charles;  Imperial College, London > Department of immunology
Willems, Luc  ;  Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
More authors (12 more) Less
Language :
English
Title :
Cell dynamics and immune response to BLV infection: a unifying model
Publication date :
2007
Journal title :
Frontiers in Bioscience: A Journal and Virtual Library
ISSN :
1093-9946
eISSN :
1093-4715
Publisher :
Frontiers in Bioscience Publications, Tampa, United States - Florida
Volume :
12
Pages :
1520-1531
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
The 6th framework program INCA project
Funders :
Fondation contre le Cancer
EC - European Commission
Bekales Foundation
F.R.S.-FNRS - Fonds de la Recherche Scientifique
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since 15 January 2013

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