The GGTCA palindrome and cognate cellular factors in trans-regulation of human immunodeficiency virus long terminal repeat by herpes simplex virus.
Molecular interactions between herpes simplex virus type 1 (HSV-1) and human immunodeficiency virus (HIV) were investigated in the promonocytic cell line U937. HSV-1-mediated activation was observed in transient expression assays with hybrid constructions containing the HIV long terminal repeat (LTR)-directed chloramphenicol acetyltransferase gene. Comparison of constructions that differ in the GGTCA palindrome located within the negative regulatory region of the LTR revealed four- to eightfold lower activation levels for the wild-type as compared to the mutant sequence. Three protein species, 37K, 59K/64K and 75K, that bind to the wild-type GGTCA palindrome were resolved in nuclear extracts of uninfected U937 cells by gel retardation and u.v.-crosslinking experiments. The 37K protein did not bind to the mutant palindrome sequence. However, a distinct 120K protein was detected. The 37K and 59K/64K binding proteins were not resolved in similar experiments performed with nuclear extracts from HSV-1-infected U937 cells but there was a novel p50 species that binds only to the wild-type palindrome sequence. These findings raise the possibility that interaction of these proteins at the GGTCA palindrome is involved in HSV-1-mediated regulation of the HIV LTR in U937 cells.
Department of Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, Baltimore 21201.
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Feng
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Kulka
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Aurelian
D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009000:Monocytes / Q000382:microbiology; D009687:Nuclear Proteins / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D018139:Simplexvirus / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger