Host control of HIV-1 parasitism in T cells by the nuclear factor of activated T cells.
Post HIV-1 entry, productive HIV-1 infection of primary T cells requires overcoming several cellular blocks to provirus establishment and replication. Activation of unknown host intracellular events overcomes such inhibitory steps and is concomitant with HIV-1 replication. We show that the transcription factor NFATc was sufficient as a cellular factor to induce a highly permissive state for HIV-1 replication in primary CD4+ T cells. NFATc overcame a blockade at reverse transcription and permitted active HIV-1 replication. Pharmacologic blockade of endogenous NFAT activity by FK506 or CsA inhibited synthesis of reverse transcription and also potently blocked HIV-1 replication. T cells therefore can become competent for HIV-1 replication by control of regulated host factors such as the NFATc transcription factor. The host mechanisms regulated by such permissivity factors are potential targets for anti-HIV-1 therapy.
Kinoshita
S
S
Department of Molecular Pharmacology, Stanford University School of Medicine, California 94305, USA.
Chen
B K
BK
Kaneshima
H
H
Nolan
G P
GP
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002455:Cell Division; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008213:Lymphocyte Activation; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000502:physiology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D014157:Transcription Factors / Q000502:physiology*; D014779:Virus Replication
D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010835:Phytohemagglutinins; D014157:Transcription Factors; D016572:Cyclosporine; D054303:HIV Reverse Transcriptase