title: Nef is required for efficient HIV-1 replication in cocultures of dendritic cells and lymphocytes.
abstract: Dendritic cells (DCs) are thought to play a crucial role in the pathogenesis of HIV-1 infection. DCs are believed to transport virus particles to lymph nodes before transfer to CD4(+) lymphocytes. We have investigated the role of Nef in these processes. HIV-1 replication was examined in human immature DC-lymphocyte cocultures and in DCs or lymphocytes separately. Using various R5-tropic and X4-tropic HIV-1 strains and their nef-deleted (Deltanef) counterparts, we show that Nef is required for optimal viral replication in immature DC-T cells clusters and in T lymphocytes. Nef exerts only a marginal role on viral replication in immature DCs alone as well as on virion capture by DCs, long-term intracellular accumulation and transmission of X4 strains to lymphocytes. We also show that wild-type and Deltanef virions are similarly processed for MHC-I restricted exogenous presentation by DCs. Taken together, these results help explain how HIV-1 Nef may affect viral spread and immune responses in the infected host.
authors.affiliation: Unité Rétrovirus et Transfert Génétique, Laboratoire d'Immunopathologie Virale, URA CNRS 1930, Institut Pasteur, 28 rue du Dr Roux, Paris Cedex 15, 75724, France.
authors.forename: C
authors.initials: C
authors.lastname: Petit
authors.forename: F
authors.initials: F
authors.lastname: Buseyne
authors.forename: C
authors.initials: C
authors.lastname: Boccaccio
authors.forename: J P
authors.initials: JP
authors.lastname: Abastado
authors.forename: J M
authors.initials: JM
authors.lastname: Heard
authors.forename: O
authors.initials: O
authors.lastname: Schwartz
mesh_terms: D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000473:pathology / Q000821:virology*; D015693:Gene Products, nef / Q000502:physiology*; D015658:HIV Infections / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000473:pathology / Q000821:virology*; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus