title: Biochemical interactions between HIV-1 integrase and reverse transcriptase.
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.
authors.affiliation: Ecological Complexity and Modeling Laboratory, University of California, Riverside, CA 92521-0124, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Chakraborty
authors.forename: Gui-Quan
authors.initials: GQ
authors.lastname: Sun
authors.forename: Laura
authors.initials: L
authors.lastname: Mustavich
authors.forename: Sheng-He
authors.initials: SH
authors.lastname: Huang
authors.forename: Bai-Lian
authors.initials: BL
authors.lastname: Li
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics; D019427:HIV Integrase / Q000737:chemistry*; D054303:HIV Reverse Transcriptase / Q000737:chemistry*; D015497:HIV-1 / Q000201:enzymology* / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D011485:Protein Binding; D048348:Reverse Transcription; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D019427:HIV Integrase; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase