title: Transcriptional regulation of HIV-1 LTR during antigen-dependent activation of primary T cells by dendritic cells.
abstract: Numerous factors are known to bind human immunodeficiency virus (HIV) long terminal repeat (LTR) and activate viral transcription, but little is known as to how they function in naturally activated T cells and to what extent their binding is relevant to HIV replication in vivo. To characterize the HIV LTR-binding factors responsible for antigen-dependent activation of HIV, we examined replication of LTR mutant viruses in CD4+ T cells activated by different stimuli. NF-kappaB or Sp1 mutant virus replicated well in CD4+ T cells activated by phorbol ester and calcium ionophore. When they were activated by antigen-pulsed dendritic cells, the replication of the Sp1-deleted virus was severely impaired in CD45RA+, but not in CD45RO+ T cell subsets that dominantly produce interleukin-2 (IL-2). Stimulation via CD3/CD28 induced a high level of IL-2 production in both T cell subsets, but Sp1-deleted virus poorly replicated in CD45RA+ subset. The level of NF-kappaB and Sp1-binding factors did not differ between these subsets. Our results suggest that additional cofactors distinct from IL-2-inducing signaling molecules are important for LTR activation during antigen-dependent T cell activation.
authors.affiliation: Department of Immunology, AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan. yyokota@nih.go.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Tsunetsugu-Yokota
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: S
authors.initials: S
authors.lastname: Yasuda
authors.forename: Z
authors.initials: Z
authors.lastname: Matsuda
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Koyanagi
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Akagawa
authors.forename: M W
authors.initials: MW
authors.lastname: Cho
authors.forename: T
authors.initials: T
authors.lastname: Takemori
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015696:Gene Products, tat / Q000235:genetics / Q000502:physiology; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D015759:Ionomycin / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D020218:Response Elements / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000821:virology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation; D014373:Tuberculin / Q000276:immunology*; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D018106:CD28 Antigens; D015696:Gene Products, tat; D007376:Interleukin-2; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D016329:Sp1 Transcription Factor; D014373:Tuberculin; D054322:tat Gene Products, Human Immunodeficiency Virus; D015759:Ionomycin; D017493:Leukocyte Common Antigens; D013755:Tetradecanoylphorbol Acetate