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Título: Studies on the MAIDS defective virus target cells
Autores: Klein, Steven J.
Fecha: 1998
Publicador: McGill University - MCGILL
Fuente:
Tipo: Electronic Thesis or Dissertation
Tema: Biology, Molecular.
Biology, Cell.
Health Sciences, Pathology.
Health Sciences, Oncology.
Descripción: Murine acquired immune deficiency syndrome (MAIDS) shares several common characteristics with human AIDS, including immunodeficiency, hypergammaglobulinemia, susceptibility to infection, both B and T cell dysfunctions, lymphadenopathy, splenomegaly and aberrant cytokine production. The etiologic agent of MAIDS has been identified as a defective retrovirus which contains major deletions in its pol and env regions but has largely maintained its gag region. The only gene product of this virus is a 60 kDa gag fusion protein, Pr60 gag, which is necessary and sufficient to induce MAIDS in susceptible mouse strains. The target cells of the MAIDS defective virus have been identified as belonging to the B cell lineage. Infection of these target cells with the MAIDS defective virus leads to their proliferation, which is required for the full development of the disease.
We undertook several approaches in order to more clearly understand the role of the MAIDS defective virus target B cell population in the development of this disease. Studies using SCID, CD4 knockout, and nude mutant mice revealed that a relatively mature B cell population is the target of the MAIDS defective virus, and that these cells can be infected in the absence of CD4+ T cells. Our knowledge of the nature of the MAIDS defective virus target B cells was furthered by the derivation of two independent MAIDS defective virus-infected B cell lines which have characteristics of both mature and immature B cells. These B cell lines were used to demonstrate an in vivo association between Pr60gag and c-Abl. Additional exploration of the Pr60gag-c-Abl interaction revealed that Pr60gag could induce a CD8+ T cell-dependant rejection of v-Abl-transformed pre-B cell lines, and increase the tumor latency of mice inoculated with Pr60 gag-expressing B16F1 melanoma cells.
Taken together, these results enhance our knowledge of the identity and role of the MAIDS defective virus target cells in the pathogenesis of this disease and propose a possible mechanism by which Pr60gag activates the disease process. As well as inducing MAIDS, Pr60 gag may also have potential positive use in cancer therapy.
Idioma: en