Role of tumor necrosis factor alpha in activation and replication of the tat-defective human immunodeficiency virus type 1.
Transcription of human immunodeficiency virus type 1 (HIV-1) depends on the function of the virus-encoded regulatory protein Tat, which interacts with the specific Tat response (TAR) element present in the leader sequence of all HIV-1 RNAs. In this study, we examined whether tumor necrosis factor alpha (TNF-alpha) can replace the requirement for a functional Tat protein. We found that TNF-alpha can induce expression of a latent, tat-defective virus and support its replication both in T cells and in primary mononuclear cells. Analysis of the transcriptional rate of the tat-defective HIV-1 transcriptional unit indicates that TNF-alpha stimulates the initiation of transcription but, in contrast to Tat protein, does not significantly reduce transcriptional polarity. Interestingly, we found that the processing of viral precursor proteins is altered in the absence of Tat. We propose that TNF-alpha-mediated induction of HIV-1 plays an essential role in the early stages of the virus life cycle and in viral latency.
Popik
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Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
Pitha
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D003673:Defective Viruses; D015870:Gene Expression; D015696:Gene Products, tat / Q000172:deficiency*; D015756:Genes, tat; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D012045:Regulatory Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000382:microbiology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014775:Virus Activation / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D014409:Tumor Necrosis Factor-alpha; D054322:tat Gene Products, Human Immunodeficiency Virus