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

• Published in: Nature medicine Vol. 5; no. 9; pp. 997 - 1003
• Main Authors: Stevenson, M, Swingler, S, Mann, A, Jacqué, J.-M, Brichacek, B, Sasseville, V.G, Williams, K, Lackner, A.A, Janoff, E.N, Wang, R, Fisher, D
• Format: Journal Article
• Language: English
• Published: United States 01-09-1999
• Subjects: Adenoviridae - genetics; Animals; Cell Line; Cells, Cultured; Chemokine CCL4; Chemokines - biosynthesis; Chemokines - genetics; Chemotaxis - drug effects; Culture Media, Conditioned; Cytokines - biosynthesis; Encephalitis, Viral - immunology; Encephalitis, Viral - virology; Gene Products, nef - genetics; Gene Products, nef - physiology; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - growth & development; HIV-1 - physiology; human immunodeficiency virus 1; Humans; Lymphocyte Activation - drug effects; Macaca; macrophage inflammatory protein 1^a; macrophage inflammatory protein 1^b; macrophage inflammatory protein 1a; macrophage inflammatory protein 1b; Macrophage Inflammatory Proteins - biosynthesis; Macrophage Inflammatory Proteins - genetics; Macrophages - immunology; Macrophages - metabolism; Macrophages - virology; Mutation; nef Gene Products, Human Immunodeficiency Virus; Nef protein; Simian Immunodeficiency Virus - drug effects; Simian Immunodeficiency Virus - growth & development; Simian Immunodeficiency Virus - physiology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - virology; Virus Replication - drug effects
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/12433

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 1alpha and 1beta, 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.