Activation of the human immunodeficiency virus type 2 enhancer is dependent on purine box and κB regulatory elements

David M. Markovitz, Michael J. Smith, John Hilfinger, Mark C. Hannibal, Bronislawa Petryniak, Gary J. Nabel

Research output: Contribution to journalArticle

Abstract

Human immunodeficiency virus type 2 (HIV-2) displays several features which distinguish it from HIV-1. Among the differences in these two viruses are the responses of their enhancer regions to T-cell activation. For example, stimulation of HIV-1 transcription is largely dependent on two κB regulatory elements. In contrast, the HIV-2 enhancer has a single κB site and contains additional cis-acting sequences responsive to induction. One of these sites, previously termed CD3R, is a purine-rich site, also called PuB1, which is responsive to stimulation of the CD3 component of the T-cell receptor complex and binds Elf-1, a member of the ets proto-oncogene family. In this report, we examine the interaction of the PuB1 site with other sites in the HIV-2 enhancer. We demonstrate that the PuB1 site confers responsiveness to T-cell activators only in cooperation with additional enhancer elements. Induction of the HIV-2 enhancer is dependent on at least two other cis-acting regulatory elements in addition to PuB1 and κB. One of these elements is another purine-rich site (PuB2), which also binds recombinant Elf-1. An adjacent region, proximal to the PuB2 ets (pets) site, shows protection in DNase footprinting experiments with extracts from Jurkat T cells. Mutation of either the κB, PuB1, PuB2, or pets site significantly reduces the response of the HIV-2 enhancer to T-cell stimulation, an effect which is mediated at the RNA level. Therefore, activation of the HIV-2 enhancer is dependent on at least four cis-acting elements, only one of which is found in HIV-1, which act in synergy with one another. Despite their sequence similarity, the organization and function of the HIV-2 enhancer have diverged considerably from those of HIV-1.

Original languageEnglish (US)
Pages (from-to)5479-5484
Number of pages6
JournalJournal of Virology
Volume66
Issue number9
StatePublished - Sep 1992
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Markovitz, D. M., Smith, M. J., Hilfinger, J., Hannibal, M. C., Petryniak, B., & Nabel, G. J. (1992). Activation of the human immunodeficiency virus type 2 enhancer is dependent on purine box and κB regulatory elements. Journal of Virology, 66(9), 5479-5484.