Selective Expression of Human Immunodeficiency Virus Nef in Specific Immune Cell Populations of Transgenic Mice Is Associated with Distinct AIDS-Like Phenotypes
| Autor: | Mathieu Goupil, Paul Jolicoeur, Véronique Dugas, Zaher Hanna, Elena Priceputu, Miriam Marquis, Chunyan Hu, Louis de Repentigny, Pavel Chrobak |
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| Rok vydání: | 2009 |
| Předmět: |
CD4-Positive T-Lymphocytes
Gene Expression Regulation Viral Immunology Population Antigens Differentiation Myelomonocytic CD11c Mice Transgenic Cell Separation Biology Microbiology Virus Mice Immune system Antigen Antigens CD Virology Animals Humans Macrophage nef Gene Products Human Immunodeficiency Virus education Acquired Immunodeficiency Syndrome education.field_of_study Macrophages virus diseases Dendritic Cells Dendritic cell CD11c Antigen Disease Models Animal Haematopoiesis Insect Science CD4 Antigens Pathogenesis and Immunity |
| Zdroj: | Journal of Virology. 83:9743-9758 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | We previously reported that CD4C/human immunodeficiency virus (HIV)Neftransgenic (Tg) mice, expressing Nef in CD4+T cells and cells of the macrophage/dendritic cell (DC) lineage, develop a severe AIDS-like disease, characterized by depletion of CD4+T cells, as well as lung, heart, and kidney diseases. In order to determine the contribution of distinct populations of hematopoietic cells to the development of this AIDS-like disease, five additional Tg strains expressing Nef through restricted cell-specific regulatory elements were generated. These Tg strains express Nef in CD4+T cells, DCs, and macrophages (CD4E/HIVNef); in CD4+T cells and DCs (mCD4/HIVNefand CD4F/HIVNef); in macrophages and DCs (CD68/HIVNef); or mainly in DCs (CD11c/HIVNef). None of these Tg strains developed significant lung and kidney diseases, suggesting the existence of as-yet-unidentified Nef-expressing cell subset(s) that are responsible for inducing organ disease in CD4C/HIVNefTg mice. Mice from all five strains developed persistent oral carriage ofCandida albicans, suggesting an impaired immune function. Only strains expressing Nef in CD4+T cells showed CD4+T-cell depletion, activation, and apoptosis. These results demonstrate that expression of Nef in CD4+T cells is the primary determinant of their depletion. Therefore, the pattern of Nef expression in specific cell population(s) largely determines the nature of the resulting pathological changes. |
| Databáze: | OpenAIRE |
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