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- Publisher Website: 10.1128/JVI.79.10.6377-6391.2005
- Scopus: eid_2-s2.0-18144416901
- PMID: 15858021
- WOS: WOS:000228814400048
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Article: The Nef-mediated AIDS-like disease of CD4C/human immunodeficiency virus transgenic mice is associated with increased Fas/FasL expression on T cells and T-cell death but is not prevented in Fas-, FasL-, tumor necrosis factor receptor 1-, or interleukin-1β-converting enzyme-deficient or Bcl2-expressing transgenic mice
Title | The Nef-mediated AIDS-like disease of CD4C/human immunodeficiency virus transgenic mice is associated with increased Fas/FasL expression on T cells and T-cell death but is not prevented in Fas-, FasL-, tumor necrosis factor receptor 1-, or interleukin-1β-converting enzyme-deficient or Bcl2-expressing transgenic mice |
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Authors | |
Issue Date | 2005 |
Citation | Journal of Virology, 2005, v. 79, n. 10, p. 6377-6391 How to Cite? |
Abstract | CD4+- and CD8+-T-cell death is a frequent immunological dysfunction associated with the development of human AIDS. We studied a murine model of AIDS, the CD4C/HIV transgenic (Tg) mouse model, to assess the importance of the apoptotic pathway in human immunodeficiency virus type 1 (HIV-1) pathogenesis. In these Tg mice, Nef is the major determinant of the disease and is expressed in immature and mature CD4+ T cells and in cells of the macrophage/myeloid lineage. We report here a novel AIDS-like phenotype: enhanced death, most likely by apoptosis (as assessed by 7-aminoactinomycin D and annexin V/propidium iodide staining), of Tg thymic and peripheral CD4+ and CD8+ T cells. The Tg CD4+ and CD8+ T cells were also more susceptible to cell death after activation in vitro in mixed lymph node (LN) cultures. However, activation-induced cell death was not higher in Tg than in non-Tg-purified CD4+ T cells. In addition, expression of Fas and FasL, assessed by flow cytometry, was increased in CD4+ and CD8+ T cells from Tg mice compared to that of non-Tg littermates. Despite the enhanced expression of Fas and FasL on Tg CD4+ and CD8+ T cells, Fas (lpr/lpr) and FasL (gld/gld) mutant CD4C/HIV Tg mice developed an AIDS-like disease indistinguishable from lpr/+ and gld/+ CD4C/HIV Tg mice, including loss of CD4+ T cells. Similarly, CD4C/HIV Tg mice faomozygous for mutations of two other genes implicated in cell death (interleukin-1β- converting enzyme [ICE], tumor necrosis factor receptor 1 [TNFR-1]) developed similar AIDS-like disease as their respective heterozygous controls. Moreover, the double-Tg mice from a cross between the Bcl2/Wehi25 and CD4C/HIV Tg mice showed no major protection against disease. These results represent genetic evidence for the dispensable role of Fas, FasL, ICE, and TNFR-1 on the development of both T-cell loss and organ disease of these Tg mice. They also provide compelling evidence on the lack of protection by Bcl2 against Tg CD4+-T-cell death. In view of the high resemblance between numerous phenotypes observed in the CD4C/HIV Tg mice and in human AIDS, our findings are likely to be relevant for the human disease. Copyright © 2005, American Society for Microbiology. All Rights Reserved. |
Persistent Identifier | http://hdl.handle.net/10722/291716 |
ISSN | 2021 Impact Factor: 6.549 2020 SCImago Journal Rankings: 2.617 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Priceputu, Elena | - |
dc.contributor.author | Rodrigue, Isabelle | - |
dc.contributor.author | Chrobak, Pavel | - |
dc.contributor.author | Poudrier, Johanne | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Hanna, Zaher | - |
dc.contributor.author | Hu, Chunyan | - |
dc.contributor.author | Kay, Denis G. | - |
dc.contributor.author | Jolicoeur, Paul | - |
dc.date.accessioned | 2020-11-17T14:54:57Z | - |
dc.date.available | 2020-11-17T14:54:57Z | - |
dc.date.issued | 2005 | - |
dc.identifier.citation | Journal of Virology, 2005, v. 79, n. 10, p. 6377-6391 | - |
dc.identifier.issn | 0022-538X | - |
dc.identifier.uri | http://hdl.handle.net/10722/291716 | - |
dc.description.abstract | CD4+- and CD8+-T-cell death is a frequent immunological dysfunction associated with the development of human AIDS. We studied a murine model of AIDS, the CD4C/HIV transgenic (Tg) mouse model, to assess the importance of the apoptotic pathway in human immunodeficiency virus type 1 (HIV-1) pathogenesis. In these Tg mice, Nef is the major determinant of the disease and is expressed in immature and mature CD4+ T cells and in cells of the macrophage/myeloid lineage. We report here a novel AIDS-like phenotype: enhanced death, most likely by apoptosis (as assessed by 7-aminoactinomycin D and annexin V/propidium iodide staining), of Tg thymic and peripheral CD4+ and CD8+ T cells. The Tg CD4+ and CD8+ T cells were also more susceptible to cell death after activation in vitro in mixed lymph node (LN) cultures. However, activation-induced cell death was not higher in Tg than in non-Tg-purified CD4+ T cells. In addition, expression of Fas and FasL, assessed by flow cytometry, was increased in CD4+ and CD8+ T cells from Tg mice compared to that of non-Tg littermates. Despite the enhanced expression of Fas and FasL on Tg CD4+ and CD8+ T cells, Fas (lpr/lpr) and FasL (gld/gld) mutant CD4C/HIV Tg mice developed an AIDS-like disease indistinguishable from lpr/+ and gld/+ CD4C/HIV Tg mice, including loss of CD4+ T cells. Similarly, CD4C/HIV Tg mice faomozygous for mutations of two other genes implicated in cell death (interleukin-1β- converting enzyme [ICE], tumor necrosis factor receptor 1 [TNFR-1]) developed similar AIDS-like disease as their respective heterozygous controls. Moreover, the double-Tg mice from a cross between the Bcl2/Wehi25 and CD4C/HIV Tg mice showed no major protection against disease. These results represent genetic evidence for the dispensable role of Fas, FasL, ICE, and TNFR-1 on the development of both T-cell loss and organ disease of these Tg mice. They also provide compelling evidence on the lack of protection by Bcl2 against Tg CD4+-T-cell death. In view of the high resemblance between numerous phenotypes observed in the CD4C/HIV Tg mice and in human AIDS, our findings are likely to be relevant for the human disease. Copyright © 2005, American Society for Microbiology. All Rights Reserved. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Virology | - |
dc.title | The Nef-mediated AIDS-like disease of CD4C/human immunodeficiency virus transgenic mice is associated with increased Fas/FasL expression on T cells and T-cell death but is not prevented in Fas-, FasL-, tumor necrosis factor receptor 1-, or interleukin-1β-converting enzyme-deficient or Bcl2-expressing transgenic mice | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1128/JVI.79.10.6377-6391.2005 | - |
dc.identifier.pmid | 15858021 | - |
dc.identifier.pmcid | PMC1091671 | - |
dc.identifier.scopus | eid_2-s2.0-18144416901 | - |
dc.identifier.volume | 79 | - |
dc.identifier.issue | 10 | - |
dc.identifier.spage | 6377 | - |
dc.identifier.epage | 6391 | - |
dc.identifier.isi | WOS:000228814400048 | - |
dc.identifier.issnl | 0022-538X | - |