1887

Abstract

The 72 kDa IE1 protein of human cytomegalovirus (HCMV) is one of a few viral regulatory proteins expressed immediately after infection of a host cell. Although it is now well-established that IE1 is a potent transcriptional activator of the human immunodeficiency virus (HIV) long terminal repeat (LTR), the identity of the nucleotide sequence responsive to IE1 remains elusive and the molecular mechanism of this interaction is not well-understood. We have constructed various LTR mutants and tested them for their ability to be activated by IE1 using transient transfection assays. Mutations in the NF-κB sites, of either a few changes in the nucleotide sequence or a deletion of the entire region, abrogated IE1-driven transactivation. Deletion of the Tat-responsive element (TAR) had no significant effect on reporter expression. Mutations in the Sp1 sites or the TATA box significantly lowered LTR activity, but this is probably due to an effect on the general transcription system, as these elements are also required for the transactivation of the LTR by many stimulators including Tat, tumour necrosis factor alpha (TNF-α), E1A/E1B and phorbol myristate acetate (PMA). In addition, gel retardation analysis demonstrated that NF-κB activity was significantly increased in human T lymphoid H9 and monocytic U937 cell lines constitutively expressing IE1. Taken together, these data suggest that NF-κB plays a central role in the IE1 transactivation of the HIV LTR.

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1996-01-01
2022-10-07
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