Silencing of human immunodeficiency virus long terminal repeat expression by an adenovirus E1a mutant.
Gene expression from the human immunodeficiency virus (HIV) long terminal repeat (LTR) is strongly stimulated by the viral tat gene. The HIV LTR is also activated by several physical and chemical agents and heterologous viral genes, including adenovirus E1a. As E1a has separable transcriptional activation and repression functions, we examined the negative regulatory effects of E1a on the expression of the HIV LTR by using a trans-dominant E1a mutant. Mutant hr5 strongly suppressed the basal activity of the LTR as well as trans-activation of the LTR by heterologous agents such as the cytomegalovirus immediate early gene or DNA-damaging agents such as mitomycin C and UV irradiation. In addition, hr5 also caused significant suppression of tat gene-mediated trans-activation. The suppression of HIV LTR expression by hr5 appears to be mediated, at least in part, by the repression of the HIV enhancer, as the activity of an enhancer test system composed of the human T-cell leukemia virus I LTR containing an HIV-1 enhancer substitution was severely repressed by hr5. Cotransfection of HIV-1 proviral DNA with hr5 DNA resulted in a significant reduction of HIV production.
Ventura
A M
AM
Institute for Molecular Virology, Saint Louis University School of Medicine, MO 63110.
Arens
M Q
MQ
Srinivasan
A
A
Chinnadurai
G
G
D017456:Adenovirus Early Proteins; D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003001:Cloning, Molecular; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D010957:Plasmids; D012091:Repetitive Sequences, Nucleic Acid; D013489:Suppression, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D017456:Adenovirus Early Proteins; D000957:Antigens, Viral, Tumor; D009856:Oncogene Proteins, Viral; D015500:Chloramphenicol O-Acetyltransferase