Distinct domains of I Kappa B- alpha inhibit human immunodeficiency virus type 1 replication through NF- Kappa B and Rev

• Published in: Journal of virology 1997-04, Vol.71 (4), p.3161-3167
• Main Authors: Wu, B, Woffendin, C, MacLachlan, L, Nabel, G J
• Format: Article
• Language: English
• Subjects: human immunodeficiency virus 1
• ISSN: 0022-538X
• DOI: 10.1128/jvi.71.4.3161-3167.1997

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