Inhibition of human immunodeficiency virus type 1 replication in vitro by a novel combination of anti-Tat single-chain intrabodies and NF-kappa B antagonists.

摘要: Human immunodeficiency virus type 1 (HIV-1) Tat, an early regulatory protein that is critical for viral gene expression and replication, transactivates the HIV-1 long terminal repeat (LTR) via its binding to transactivation response element (TAR) and, along with other cellular factors, increases transcription initiation elongation. Tat also superactivates promoter through a TAR-independent mechanism, including tumor necrosis factor alpha-induced kinase C (PKC)-dependent activation of NF-kappa B, inhibitors B cooperatively down-regulate this Tat-mediated LTR superactivation. In study, combined pharmacologic genetic strategy using two PKC (NF-kappa B) inhibitors, pentoxifylline (PTX) Go-6976, stably expressed anti-Tat single-chain intracellular antibody (sFv intrabody) was employed obtain cooperative inhibition both LTR-driven replication. Treatment cells PTX Go-6976 resulted in addition, use sFv intrabodies retained latent state as 45 days. The treatment more durable replication than seen alone or alone. Together, these results suggest future clinical therapy trials, like one reported here may improve survival transduced prolong benefit.