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Journal of Virology, October 2009, p. 9743-9758, Vol. 83, No. 19
0022-538X/09/$08.00+0     doi:10.1128/JVI.00125-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Selective Expression of Human Immunodeficiency Virus Nef in Specific Immune Cell Populations of Transgenic Mice Is Associated with Distinct AIDS-Like Phenotypes ^,

Zaher Hanna,^1,2,5* Elena Priceputu,¹ Pavel Chrobak,¹ Chunyan Hu,¹ Véronique Dugas,³ Mathieu Goupil,³ Miriam Marquis,³ Louis de Repentigny,^3,4 and Paul Jolicoeur^1,3,5*

Laboratory of Molecular Biology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada,¹ Departments of Medicine,² Microbiology and Immunology, University of Montreal,³ Sainte-Justine Hospital, Montreal, Quebec H3C 3J7, Canada,⁴ Division of Experimental Medicine, McGill University, Montreal, Quebec H3G 1A4, Canada⁵

Received 19 January 2009/ Accepted 2 July 2009

We previously reported that CD4C/human immunodeficiency virus (HIV)^Nef transgenic (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/HIV^Nef); in CD4⁺ T cells and DCs (mCD4/HIV^Nef and CD4F/HIV^Nef); in macrophages and DCs (CD68/HIV^Nef); or mainly in DCs (CD11c/HIV^Nef). 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/HIV^Nef Tg mice. Mice from all five strains developed persistent oral carriage of Candida 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.

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* Corresponding author. Mailing address for P. Jolicoeur: Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada. Phone: (514) 987-5569. Fax: (514) 987-5794. E-mail: jolicop{at}ircm.qc.ca. Mailing address for Z. Hanna: Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada. Phone: (514) 987-5571. Fax: (514) 987-5794. E-mail: hannaz{at}ircm.qc.ca

Published ahead of print on 15 July 2009.

Supplemental material for this article may be found at http://jvi.asm.org/.

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Journal of Virology, October 2009, p. 9743-9758, Vol. 83, No. 19
0022-538X/09/$08.00+0     doi:10.1128/JVI.00125-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Rahim, M. M. A., Chrobak, P., Hu, C., Hanna, Z., Jolicoeur, P. (2009). Adult AIDS-Like Disease in a Novel Inducible Human Immunodeficiency Virus Type 1 Nef Transgenic Mouse Model: CD4+ T-Cell Activation Is Nef Dependent and Can Occur in the Absence of Lymphophenia. J. Virol. 83: 11830-11846 [Abstract] [Full Text]