A discrete cis element in the human immunodeficiency virus long terminal repeat mediates synergistic trans activation by cytomegalovirus immediate-early proteins
- PMID: 1682509
- PMCID: PMC250754
- DOI: 10.1128/JVI.65.12.6735-6742.1991
A discrete cis element in the human immunodeficiency virus long terminal repeat mediates synergistic trans activation by cytomegalovirus immediate-early proteins
Abstract
The major immediate-early (IE) promoter of human cytomegalovirus directs the expression of several differentially spliced and polyadenylated mRNAs that encode isoformic proteins with apparent molecular masses of 55, 72, and 86 kDa. All of these proteins are potent transcriptional regulatory proteins. We are interested in the collateral interactions between human cytomegalovirus and human immunodeficiency virus (HIV) in the context of dual infection of a cell. The roles of the specific IE protein isoforms and their respective response elements involved in trans activation of the HIV long terminal repeat (LTR) are not known. Here we present evidence that major IE proteins IE86, IE72, and IE55 are capable of trans-activating the HIV LTR in a T-cell line, HUT-78. The IE55 isoform noncooperatively stimulates the HIV LTR in the presence of either isoform IE72 or IE86. Interactions between isoforms IE72 and IE86, however, result in strong synergistic activation of the LTR. Our results suggest that a specific 155-amino-acid protein domain that is unique for the IE86 protein participates in this synergic interaction. Point mutational analysis of the LTR identified a distinct cis-acting target site, located between nucleotide positions -174 and -163, that mediates exclusively synergistic trans activation by the IE72 and IE86 proteins. Finally, this study underscores the role of a cellular intermediate(s) for communicating the synergic interactions between two IE trans activators.
Similar articles
-
Interaction of the 72-kilodalton human cytomegalovirus IE1 gene product with E2F1 coincides with E2F-dependent activation of dihydrofolate reductase transcription.J Virol. 1995 Dec;69(12):7759-67. doi: 10.1128/JVI.69.12.7759-7767.1995. J Virol. 1995. PMID: 7494286 Free PMC article.
-
An isoform variant of the cytomegalovirus immediate-early auto repressor functions as a transcriptional activator.Virology. 1992 Jun;188(2):518-29. doi: 10.1016/0042-6822(92)90506-k. Virology. 1992. PMID: 1316671
-
Transcription factor Sp1 mediates cell-specific trans-activation of the human cytomegalovirus DNA polymerase gene promoter by immediate-early protein IE86 in glioblastoma U373MG cells.J Virol. 1998 Jan;72(1):236-44. doi: 10.1128/JVI.72.1.236-244.1998. J Virol. 1998. PMID: 9420220 Free PMC article.
-
Identification of human cytomegalovirus target sequences in the human immunodeficiency virus long terminal repeat. Potential role of IE2-86 binding to sequences between -120 and -20 in promoter transactivation.J Hum Virol. 1999 Mar-Apr;2(2):81-90. J Hum Virol. 1999. PMID: 10225210
-
Separate DNA elements containing ATF/CREB and IE86 binding sites differentially regulate the human cytomegalovirus UL112-113 promoter at early and late times in the infection.J Virol. 1998 Apr;72(4):2697-707. doi: 10.1128/JVI.72.4.2697-2707.1998. J Virol. 1998. PMID: 9525587 Free PMC article.
Cited by
-
In vivo and in vitro analysis of transcriptional activation mediated by the human cytomegalovirus major immediate-early proteins.Mol Cell Biol. 1993 Feb;13(2):1238-50. doi: 10.1128/mcb.13.2.1238-1250.1993. Mol Cell Biol. 1993. PMID: 8423789 Free PMC article.
-
Human cytomegalovirus immediate-early 2 (IE2) protein can transactivate the human hsp70 promoter by alleviation of Dr1-mediated repression.J Virol. 1996 Jun;70(6):4028-37. doi: 10.1128/JVI.70.6.4028-4037.1996. J Virol. 1996. PMID: 8648740 Free PMC article.
-
Strain variations in single amino acids of the 86-kilodalton human cytomegalovirus major immediate-early protein (IE2) affect its functional and biochemical properties: implications of dynamic protein conformation.J Virol. 2003 Apr;77(8):4760-72. doi: 10.1128/jvi.77.8.4760-4772.2003. J Virol. 2003. PMID: 12663783 Free PMC article.
-
Analysis of splice variants of the immediate-early 1 region of human cytomegalovirus.J Virol. 2004 Aug;78(15):8191-200. doi: 10.1128/JVI.78.15.8191-8200.2004. J Virol. 2004. PMID: 15254190 Free PMC article.
-
Interaction of the 72-kilodalton human cytomegalovirus IE1 gene product with E2F1 coincides with E2F-dependent activation of dihydrofolate reductase transcription.J Virol. 1995 Dec;69(12):7759-67. doi: 10.1128/JVI.69.12.7759-7767.1995. J Virol. 1995. PMID: 7494286 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources