Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.
TRANSCRIPTIONAL REGULATION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1
Vaccines 88. New Chemical and Genetic Approaches to Vaccination: Prevention of AIDS and Other Viral, Bacterial, and Parasitic Diseases. Ginsberg H et al, eds. New York, Cold Spring Harbor Laboratory, p. 283-90, 1988.. Unique Identifier : AIDSLINE ICDB/89649770 Peterlin BM; Calman AF; Kao SY; Selby MJ; Tong-Starksen SE; Luciw PA; Howard Hughes Medical Inst., Dept. of Medicine, Univ. of; California, San Francisco, CA 94143
Abstract:
The present work demonstrated that T-cell-activation signals increase transcription from the long terminal repeat (LTR) of the San Francisco-2 isolate of HIV, designated here as HIV-1-LTR. It also was determined that the trans-activator (tat) acts as a transcriptional antiterminator that allows transcripts initiating from the HIV-1 cap site to elongate through the trans-acting responsive element (TAR) sequences efficiently. These effects of T-cell activation and trans-activation of tat were multiplicative and resulted in high levels of viral gene expression in Jurkat cells cotransfected with HIV-1-LTR-chloramphenicol acetyltransferase and SV40-synthetic tat gene constructs. The results provide a molecular description of HIV infection. HIV enters CD4 cells, which are arrested in G0 phase. The transcriptional enhancer is inactive, and transcripts initiated in quiescent cells do not elongate through TAR. Only through activation of HIV-1 transcription, which results from cellular activation or trans-activation by other DNA viruses, are some full-length transcripts made. The tat is synthesized and acts at TAR to relieve the block to transcriptional elongation. Thus, at some threshold level of transcriptional initiation and antitermination of tat, viral gene expression begins and is greatly amplified. Viral replication ensues, many progeny viruses are released, and additional T cells are infected. Viral genes are expressed and result in cytopathology through an unknown mechanism. Vacuolization and formation of syncytia are observed in T cells infected in vitro. When sufficient numbers of T cells are infected and activated, virus is produced, T cells are killed, and symptoms of AIDS or AIDS-related complex appear. Analyses of the molecular events leading to HIV-1 activation and trans-activation by tat will reveal specific targets for future therapeutic intervention. (16 Refs)
Keywords: Cell Line Cytopathogenic Effect, Viral CD4-Positive T-Lymphocytes/MICROBIOLOGY DNA, Viral/GENETICS Gene Expression Regulation Human HIV-1/*GENETICS Terminator Regions (Genetics) Transcription Factors/GENETICS *Transcription, Genetic Transfection Virus Replication MEETING PAPER
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Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.
