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HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages

Nature Medicine volume 5, pages 997–1003 (1999)Cite this article

Abstract

Infection of macrophage lineage cells is a feature of primate lentivirus replication, and several properties of primate lentiviruses seem to have evolved to promote the infection of macrophages. Here we demonstrate that the accessory gene product Nef induces the production of two CC-chemokines, macrophage inflammatory proteins 1α and 1β, by HIV-1-infected macrophages. Adenovirus-mediated expression of Nef in primary macrophages was sufficient for chemokine induction. Supernatants from Nef-expressing macrophages induced both the chemotaxis and activation of resting T lymphocytes, permitting productive HIV-1 infection. These results indicate a role for Nef in lymphocyte recruitment and activation at sites of virus replication.

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Figure 1: HIV-1 Nef influences CC-chemokine production by HIV-1-infected macrophages.
Figure 2: Nef expression is sufficient for induction of CC-chemokine expression.
Figure 3: Induction of lymphocyte chemotaxis by supernatants from HIV-1-infected and Nef-expressing macrophage cultures.
Figure 4: Induction of lymphocyte activation and 'permissiveness' to HIV-1 infection by Nef-expressing macrophage supernatants.
Figure 5: β chemokine expression associated with SIV-infected macrophages.

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Acknowledgements

We thank E. Thomas, S. Dupont and B. Blais for technical assistance, H.E. Gendelman for assistance with macrophage culture, B. Mellor and K. Toohey for graphics support and N. Bakker for manuscript preparation. This work was supported by National Institutes of Health grants, NS30769 and NS35732 to A.L., AI39445 and HL96008 to E.J., AI37475, HL57880 and RR11589 to M.S. and by funding from the Edward Jenner Institute for Vaccine Research (M.S.).

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Authors and Affiliations

  1. University of Massachusetts Medical Center, Program in Molecular Medicine, 373 Plantation Street, Worcester, 01605, Massachusetts, USA

    S. Swingler, A. Mann, J.-M. Jacqué, B. Brichacek & M. Stevenson

  2. University of Massachusetts Medical Center, Molecular Genetics and Microbiology, 373 Plantation Street, Worcester, 01605, Massachusetts, USA

    A. Mann, B. Brichacek & M. Stevenson

  3. New England Regional Primate Research Center, Harvard Medical School, Southborough, 01772, Massachusetts, USA

    V.G. Sasseville, K. Williams & A.A. Lackner

  4. Veterans Administration Medical Center, 1 Veterans Drive, Minneapolis, 55417, Minnesota, USA

    E.N. Janoff

  5. Department of Cardiology, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, 01655, Massachusetts, USA

    R. Wang & D. Fisher

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Swingler, S., Mann, A., Jacqué, JM. et al. HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages. Nat Med 5, 997–1003 (1999). https://doi.org/10.1038/12433

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