The role of upstream U3 sequences in HIV-1 replication and CD4+ T cell depletion in human lymphoid tissue ex vivo.
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.
Münch
Jan
J
Department of Virology, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Rajan
Devi
D
Rücker
Elke
E
Wildum
Steffen
S
Adam
Nadia
N
Kirchhoff
Frank
F
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
D015693:Gene Products, nef; D016655:HIV Core Protein p24; D054311:nef Gene Products, Human Immunodeficiency Virus; D054303:HIV Reverse Transcriptase