What question did this study set out to answer?

Investigate whether phosphorylation-defective transdominant mutants of I kappa B alpha can inhibit the synergistic activation of HIV-1 gene expression and viral replication driven by Tat and TNF-alpha.

September 1, 1996Journal of VirologyOpen Access

Transdominant mutants of I kappa B alpha block Tat-tumor necrosis factor synergistic activation of human immunodeficiency virus type 1 gene expression and virus multiplication

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Authors

PBPierre BeauparlantJewish General Hospital HKHakju KwonABL Bio (South Korea)MCM ClarkeAlbert Einstein College of Medicine

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Implication

In vitro study demonstrates that transdominant I kappa B alpha mutants block Tat-TNF-alpha synergistic activation and viral replication, suggesting an NF-kappa B-targeted anti-HIV strategy.

Key Points

Investigate whether phosphorylation-defective transdominant mutants of I kappa B alpha can inhibit the synergistic activation of HIV-1 gene expression and viral replication driven by Tat and TNF-alpha.
Assayed HIV-1 long terminal repeat (LTR) transactivation in Jurkat T cells following stimulation with TNF-alpha, wild-type or mutated Tat (R52Q, R53Q), and modified TAR elements.
Tested wild-type and phosphorylation-defective I kappa B alpha mutants (S32A, S36A, S283A, T291A, T299A) for protein stability and inhibition of LTR expression.
Assessed HIV-1 multiplication in a single-cycle infection model in Cos-1 cells by measuring viral mRNA through Northern blotting and viral protein production.
Tat and TNF-alpha synergistically induced a 50- to 70-fold stimulation of HIV-1 LTR-driven gene expression, requiring an intact enhancer and Tat-TAR interaction.
N-terminal I kappa B alpha mutant (S32A, S36A) resisted degradation (half-life > 4 hours) and inhibited synergistic LTR transactivation at least five times more effectively than wild-type I kappa B alpha.
Expression of the S32A/S36A mutant substantially blocked HIV-1 viral mRNA accumulation and protein production in Cos-1 cells.

Cite This Study

Beauparlant et al. (1996) studied this question.

synapsesocial.com/papers/6a18e8bd673175fe754b0cd3 https://doi.org/10.1128/jvi.70.9.5777-5785.1996

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Implication

In vitro study demonstrates that transdominant I kappa B alpha mutants block Tat-TNF-alpha synergistic activation and viral replication, suggesting an NF-kappa B-targeted anti-HIV strategy.

Transdominant mutants of I kappa B alpha block Tat-tumor necrosis factor synergistic activation of human immunodeficiency virus type 1 gene expression and virus multiplication

Discussion

Member takes

Implication

Key Points

Cite This Study

Transdominant mutants of I kappa B alpha block Tat-tumor necrosis factor synergistic activation of human immunodeficiency virus type 1 gene expression and virus multiplication

Discussion

Member takes

Implication

Key Points

Cite This Study

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