Biochemical interactions between HIV‐1 integrase and reverse transcriptase. Issue 5 (25th December 2012)

• Record Type: Journal Article
• Authors: Chakraborty, Amit; Sun, Gui-Quan; Mustavich, Laura; Huang, Sheng-He; Li, Bai-Lian
• Is Part Of: FEBS letters. Volume 587:Issue 5(2013)
• Page Start: 425
• Page End: 429
• Publication Date: 2012-12-25
• Subjects: Provirus -- Reverse transcription -- Pre-integration complex -- Integration reaction; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2012.12.007
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Human immunodeficiency virus (HIV) infection yields a high level of non‐integrated viral DNA in the infected cells and up to 99% of total viral DNA can be capable of transcription. This capability of non‐integrated viral DNA is reducing the efficacy of anti‐HIV drug development approaches that solely focus on the integration reactions of viral replication. Using kinetic modeling, we show the transient coordinated regulation of viral DNA production by retrovirus‐encoded interacting enzymes reverse transcriptase (RT) and integrase (IN), and thus we identify a possible mechanism for reducing overall efficiency of viral replication. The results indicate that both IN·RT and IN·DNA complexes and their formation rates affect RT processivity and thereby the viral DNA expression level within the pre‐integration complex. Abstract : ► Interactions between HIV‐1 reverse transcriptase and integrase have been modeled. ► The model illustrates coordinated regulation of viral DNA production. ► High availability of non‐integrated DNA depends on the nature of interactions. ► The indirect mode of interaction provides a strong negative feedback. ► IN·RT and IN·DNA complexes and their formation rates affect RT processivity.