Distinct domains of IκB-α inhibit human immunodeficiency virus type 1 replication through NF-κB and Rev

Bei Yue Wu, Clive Woffendin, Ian MacLachlan, Gary J. Nabel

Research output: Contribution to journalArticlepeer-review

Abstract

Among the regulators of human immunodeficiency virus (HIV) replication is the cellular transcription factor NF-κB, whose activity is regulated through inhibition by IκB family members. We have shown previously that IκB-α inhibits HIV type 1 (HIV-1) replication, and unexpectedly, IκB-α was found both to suppress HIV-1 transcription and to inhibit Rev function. The relative contributions and specificities of these mechanisms to HIV replication were unknown. Here, we report that the region of IκB-α which blocks Rev function is separable from that required for inhibition of NF- κB. Molecular mutagenesis revealed that the N terminus of IκB-α is required for inhibition of Rev function, whereas mutants lacking the N terminus retained the ability to inhibit NF-κB function. Interestingly, the nuclear export sequence of IκB-α was not required for inhibition of Rev or NF-κB function in mammalian transfection assays. Conversely, the C terminus of IκB-α was not required for the inhibition of Rev, while deletion of this region resulted in a loss of NF-κB inhibition. Another IκB family member with a distinct amino-terminal sequence, IκB-β, inhibited NF-κB but not Rev function. These studies indicate that the inhibition of Rev by IκB-α is independent of NF-κB. Mutants defective in inhibition of either Rev or NF- κB retained the ability to inhibit HIV-1 replication, suggesting that both functions may contribute to the inhibition of HIV replication by IκB-α.

Original languageEnglish (US)
Pages (from-to)3161-3167
Number of pages7
JournalJournal of Virology
Volume71
Issue number4
StatePublished - Apr 1997
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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