Central nervous system-derived cells express a κB-binding activity that enhances human immunodeficiency virus type 1 transcription in vitro and facilitates TAR-independent transactivation by Tat

J. Paul Taylor, Roger J. Pomerantz, Ganesh V. Raj, Fatah Kashanchi, John N. Brady, Shohreh Amini, Kamel Khalili

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

The Tat protein of human immunodeficiency virus type 1 (HIV-1) is a potent activator of long terminal repeat-directed transcription. While in most cell types, activation requires interaction of Tat with the unusual transcription element TAR, astrocytic glial cells support TAR-independent transactivation of HIV-1 transcription by Tat. This alternative pathway of Tat activation is mediated by the viral enhancer, a κB domain capable of binding the prototypical form of the transcription factor nuclear factor kappa B (NF- κB) present in many cell types, including T lymphocytes. Tat transactivation mediated by the κB domain is sufficient to allow replication of TAR-deleted mutant HIV-1 in astrocytes. The present study demonstrates the existence of κB-specific binding factors present in human glial astrocytes that differ from prototypical NF-κB. The novel astrocyte-derived κB-binding activity is retained on an HIV-1 Tat affinity column, while prototypical NF-κB from Jurkat T cells is not. In vitro transcription studies demonstrate that astrocyte-derived κB-binding factors activate transcription of the HIV-1 long terminal repeat and that this activation is dependent on the κB domain. Moreover, TAR-independent transactivation of HIV-1 transcription is reproduced in vitro in an astrocyte factor-dependent manner which correlates with κB-binding activity. The importance of the central nervous system- enriched κB transcription factor in the regulation of HIV-1 expression is discussed.

Original languageEnglish (US)
Pages (from-to)3971-3981
Number of pages11
JournalJournal of virology
Volume68
Issue number6
DOIs
StatePublished - Jun 1994

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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