Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
DNA VIRAL TRANS-ACTIVATION OF THE HUMAN IMMUNODEFICIENCY VIRUS LONG TERMINAL REPEAT SEQUENCE
Vaccines 87. Modern Approaches to New Vaccines: Prevention of AIDS and Other Viral, Bacterial, and Parasitic Diseases. Chanock RM et al, eds. New York, Cold Spring Harbor Laboratory, p. 154-8, 1987.. Unique Identifier : AIDSLINE ICDB/88647970 Gendelman HE; Martin MA; Lab. of Molecular Biology, NIAID, NIH, Bethesda, MD 20892
Abstract:
Acquired immune deficiency syndrome (AIDS) is etiologically linked to a retrovirus, the human immunodeficiency virus (HIV), that can replicate in exposed individuals for long periods in the absence of clinical disease. As many HIV-infected individuals harbor a variety of microorganisms, the possibility exists that some of these pathogens can act as cofactors capable of stimulating HIV expression and thereby accelerate the disease process. One class of cofactors, DNA viruses, were investigated for their ability to augment gene expression of the HIV long terminal repeat (LTR). These viral cofactors include members of the papovavirus and herpesvirus families and encode gene products that stimulate HIV gene expression in specific host cells. The implications of this observation for viral latency and the course of HIV disease are discussed. The capacity of DNA viruses to augment expression of HIV was investigated in cotransfection experiments employing the HIV LTR linked to chloramphenicol acetyl transferase (CAT) gene and a variety of cloned viral DNAs. The HIV LTR-CAT construct was generated from an integrated proviral DNA clone of the lymphadenopathy-associated virus (LAV). The HIV LTR-CAT DNA, salmon sperm DNA, pAR(tat), and/or the DNA viral plasmids were cotransfected into a variety of cell lines by calcium precipitation, and assays for CAT activities were performed. The SW480 colon carcinoma cell line was chosen as the recipient cell in initial cotransfection experiments because of its exquisite sensitivity to DNA transfection. High levels of CAT activity were demonstrated following cotransfection of HIV LTR-CAT and pAR(tat) DNAs as compared with the transfection of HIV LTR-CAT DNA alone. The influence of the host cells on the stimulatory effects of tat or heterologous viral regulatory proteins on the HIV LTR was examined in four additional cell lines. The cotransfected HIV tat plasmid produced the highest level of CAT activity in all cell lines examined (SW480, HeLa, CV-1, COS, A-204). Interruption of the early regions of BKV (entire BK virus) and JC virus DNAs resulted in a twofold reduction in the levels of CAT expression compared with cells transfected with intact papovavirus genomes. This demonstrated that heterologous viral DNAs can increase expression of the HIV promoter and that this effect is dependent on the host-cell milieu. When the HIV tat gene was introduced with the heterologous viral DNA trans-activators, augmented stimulation of the HIV promoter was seen. (15 Refs)
Keywords: Acquired Immunodeficiency Syndrome/MICROBIOLOGY Cytopathogenic Effect, Viral DNA, Viral/*GENETICS Gene Expression Regulation Human HIV/*GENETICS Promoter Regions (Genetics) *Repetitive Sequences, Nucleic Acid *Terminator Regions (Genetics) Transcription Factors/*GENETICS MEETING PAPER
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Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
