Transcriptional regulation of HIV-1 LTR during antigen-dependent activation of primary T cells by dendritic cells.
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.
Tsunetsugu-Yokota
Y
Y
Department of Immunology, AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan. yyokota@nih.go.jp
Kato
T
T
Yasuda
S
S
Matsuda
Z
Z
Suzuki
Y
Y
Koyanagi
Y
Y
Yamamoto
N
N
Akagawa
K
K
Cho
M W
MW
Takemori
T
T
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
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