HIV-1 IN catalyzes two reactions.  These reactions use the same integrase active site. 

3' Processing Reaction:

Processing takes place in the cytoplasm of the infected cell after reverse transcription of the viral RNA.¹ In this 3' processing step, IN removes two nucleotides from each of the 3' ends of the viral cDNA.  These two nucleotides are just 3' of the conserved dinucleotides, 5' CA 3'. ⁷  Mutations of this CA/TG result in a greater than 10⁵ fold loss in integration.³  Thus, this reaction is site specific.  This processing step is shown below. This reaction takes place via a preintegration complex, as represented by grey ovals.  HIV-1 may be recruited to the insertion site by the preintegration complex and protein-protein interactions.⁷

Recreated from Heuer & Brown, 1998.⁵

Joining Reaction (Strand Transfer):

The joining reaction takes place after the preintegration complex and the processed viral DNA migrate to the nucleus.¹  The preintegration complex dissociates and the processed viral DNA enters into the nucleus. As shown above, this second reaction joins the CA 3'OH groups of the viral DNA to the target host DNA.  This is accomplished by the viral DNA's 3'OHes attacking the phosphodiester bonds of the host DNA.  The phosphates that are attacked are generally 5 base pairs apart on the two host DNA strands.⁷  The viral DNA ends are inserted into opposite strands of the host DNA in a direct transesterification reaction.⁴  Integration of the viral DNA is not site specific but may be due to the DNA structure.⁷  Bent DNA such as sites exposed on the major groove on nucleosomes are frequently targeted insertion sites.³  Other studies suggest insertion occurs near active transcription sites.⁷  Protein studies have suggested that the core domain is responsible for determining the insertion site.³  After insertion, gaps are left on the 5' ends of the viral DNA.  The repair of these gaps is believed to be carried out by host mechanisms.⁷

Introduction    N-terminal domain    Core domain    C-terminal domain    References 

Angela Marks Department of Chemistry marksaf@uwec.edu Updated: Sunday, December 13, 1998