title: The role of upstream U3 sequences in HIV-1 replication and CD4+ T cell depletion in human lymphoid tissue ex vivo.
abstract: The LTRs of all primate lentiviruses contain long U3 regions overlapping the nef gene. To assess the relevance of the modulatory U3 region for HIV-1 replication, we inactivated the T-rich region, the Polypurine tract and attachment (att) sequences in nef by silent mutations and inserted intact cis-regulatory elements just upstream of the core enhancer. These modifications severely truncated the U3 region and eliminated the nef overlap. The resulting HIV-1 mutants expressed functional Nef, replicated efficiently and caused CD4+ T cell depletion in ex vivo-infected lymphoid tissue suggesting that the modulatory U3 region might not be essential for efficient HIV-1 gene expression and AIDS pathogenesis.
authors.affiliation: Department of Virology, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Münch
authors.forename: Devi
authors.initials: D
authors.lastname: Rajan
authors.forename: Elke
authors.initials: E
authors.lastname: Rücker
authors.forename: Steffen
authors.initials: S
authors.lastname: Wildum
authors.forename: Nadia
authors.initials: N
authors.lastname: Adam
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
mesh_terms: D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D015693:Gene Products, nef / Q000032:analysis; D015754:Genes, nef; D016655:HIV Core Protein p24 / Q000032:analysis; D016325:HIV Long Terminal Repeat / Q000235:genetics* / Q000502:physiology; D054303:HIV Reverse Transcriptase / Q000032:analysis; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D009154:Mutation; D014066:Palatine Tonsil / Q000821:virology*; D050436:Regulatory Elements, Transcriptional; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015693:Gene Products, nef; D016655:HIV Core Protein p24; D054311:nef Gene Products, Human Immunodeficiency Virus; D054303:HIV Reverse Transcriptase