A discrete cis element in the human immunodeficiency virus long terminal repeat mediates synergistic trans activation by cytomegalovirus immediate-Early proteins

Peter Ghazal, James Young, Emi Giulietti, Cordell Demattei, Joseph Garcia, Richard Gaynor, Richard M. Stenberg, Jay A. Nelson

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)6735-6742
Number of pages8
JournalJournal of Virology
Volume65
Issue number12
StatePublished - Dec 1991

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HIV Long Terminal Repeat
Cytomegalovirus
terminal repeat sequences
Human immunodeficiency virus
transcriptional activation
Protein Isoforms
Immediate-Early Proteins
Human herpesvirus 5
Terminal Repeat Sequences
Proteins
proteins
Trans-Activators
Response Elements
protein isoforms
response elements
regulatory proteins
messenger RNA
Nucleotides
cytomegalovirus immediate-early proteins
HIV

ASJC Scopus subject areas

  • Immunology

Cite this

A discrete cis element in the human immunodeficiency virus long terminal repeat mediates synergistic trans activation by cytomegalovirus immediate-Early proteins. / Ghazal, Peter; Young, James; Giulietti, Emi; Demattei, Cordell; Garcia, Joseph; Gaynor, Richard; Stenberg, Richard M.; Nelson, Jay A.

In: Journal of Virology, Vol. 65, No. 12, 12.1991, p. 6735-6742.

Research output: Contribution to journalArticle

Ghazal, P, Young, J, Giulietti, E, Demattei, C, Garcia, J, Gaynor, R, Stenberg, RM & Nelson, JA 1991, 'A discrete cis element in the human immunodeficiency virus long terminal repeat mediates synergistic trans activation by cytomegalovirus immediate-Early proteins', Journal of Virology, vol. 65, no. 12, pp. 6735-6742.
Ghazal, Peter ; Young, James ; Giulietti, Emi ; Demattei, Cordell ; Garcia, Joseph ; Gaynor, Richard ; Stenberg, Richard M. ; Nelson, Jay A. / A discrete cis element in the human immunodeficiency virus long terminal repeat mediates synergistic trans activation by cytomegalovirus immediate-Early proteins. In: Journal of Virology. 1991 ; Vol. 65, No. 12. pp. 6735-6742.
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