title: The inability to disrupt the immunological synapse between infected human T cells and APCs distinguishes HIV-1 from most other primate lentiviruses.
abstract: Viruses that infect T cells, including those of the lentivirus genus, such as HIV-1, modulate the responsiveness of infected T cells to stimulation by interacting APCs in a manner that renders the T cells more permissive for viral replication. HIV-1 and other primate lentiviruses use their Nef proteins to manipulate the T cell/APC contact zone, the immunological synapse (IS). It is known that primate lentiviral Nef proteins differ substantially in their ability to modulate cell surface expression of the TCR-CD3 and CD28 receptors critical for the formation and function of the IS. However, the impact of these differences in Nef function on the interaction and communication between virally infected T cells and primary APCs has not been investigated. Here we have used primary human cells to show that Nef proteins encoded by HIV-2 and most SIVs, which downmodulate cell surface expression of TCR-CD3, disrupt formation of the IS between infected T cells and Ag-presenting macrophages or DCs. In contrast, nef alleles from HIV-1 and its simian precursor SIVcpz failed to suppress synapse formation and events downstream of TCR signaling. Our data suggest that most primate lentiviruses disrupt communication between virally infected CD4+ Th cells and APCs, whereas HIV-1 and its SIV precursor have largely lost this capability. The resulting differences in the levels of T cell activation and apoptosis may play a role in the pathogenesis of AIDS.
authors.affiliation: Institute of Molecular Virology, University of Ulm, Albert-Einstein-Allee 11, Ulm, Germany.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Arhel
authors.forename: Martin
authors.initials: M
authors.lastname: Lehmann
authors.forename: Karen
authors.initials: K
authors.lastname: Clauss
authors.forename: G Ulrich
authors.initials: GU
authors.lastname: Nienhaus
authors.forename: Vincent
authors.initials: V
authors.lastname: Piguet
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
mesh_terms: D000483:Alleles; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology*; D017958:Lentiviruses, Primate / Q000235:genetics / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism; D011323:Primates; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D016608:Talin / Q000235:genetics / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D016608:Talin; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)