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HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages

Nature Medicine volume 9, pages 191–197 (2003)Cite this article

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Abstract

Immature dendritic cells are among the first cells infected by retroviruses after mucosal exposure. We explored the effects of human immunodeficiency virus-1 (HIV-1) and its Tat transactivator on these primary antigen-presenting cells using DNA microarray analysis and functional assays. We found that HIV-1 infection or Tat expression induces interferon (IFN)-responsive gene expression in immature human dendritic cells without inducing maturation. Among the induced gene products are chemokines that recruit activated T cells and macrophages, the ultimate target cells for the virus. Dendritic cells in the lymph nodes of macaques infected with simian immunodeficiency virus (SIV) have elevated levels of monocyte chemoattractant protein 2 (MCP-2), demonstrating that chemokine induction also occurs during retroviral infection in vivo. These results show that HIV-1 Tat reprograms host dendritic cell gene expression to facilitate expansion of HIV-1 infection.

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Figure 1: Tat expression and HIV-1 infection in iDC.
Figure 2: Expression analysis of primary iDC infected with HIV-1BAL and adeno-Tat.
Figure 3: Secretion of chemokines from primary dendritic cells expressing Tat.
Figure 4: MCP-2 expression and SIV infection in axillary lymph nodes.
Figure 5: a–b, Chemotaxis of monocytes (a) and activated T cells (b) induced by supernatants of iDC infected with adeno-Tat and HIV-1.

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Acknowledgements

We thank J.-S. Lee of the Harvard Gene Therapy Initiative Vector Core, supported in part by the Association Française contre les Myopathies, for providing the adeno-LacZ and adeno-Tat viruses; M. Stevenson for the adeno-Nef virus; D. Pokholok, G. Nau, J. Richmond, A. Schlesinger and E. Jennings for discussion and help with data analysis. This work was supported by NIH grants AI41365, AI44476, RR00169 and RR14555.

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Authors and Affiliations

  1. Department of Medicine, and Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Elena Izmailova, Frederic M.N. Bertley & Anna Aldovini

  2. Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA

    Qian Huang & Richard A. Young

  3. California National Primate Research Center, University of California, Davis, California, USA

    Norbert Makori & Christopher J. Miller

  4. Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, and Center for Comparative Medicine, University of California, Davis, California, USA

    Christopher J. Miller

  5. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Richard A. Young

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Correspondence to Anna Aldovini.

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Izmailova, E., Bertley, F., Huang, Q. et al. HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages. Nat Med 9, 191–197 (2003). https://doi.org/10.1038/nm822

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