Integration of a reverse transcribed DNA copy of the HIV viral genome into the host chromosome is essential for virus replication. This process is catalyzed by the virally encoded protein integrase. The catalytic activities, which involve DNA cutting and joining steps, have been recapitulated in vitro using recombinant integrase and synthetic DNA substrates. Biochemical and biophysical studies of these model reactions have been pivotal in advancing our understanding of mechanistic details for how IN interacts with viral and target DNAs, and are the focus of the present review.
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http://dx.doi.org/10.3390/v1030713 | DOI Listing |
Antimicrob Agents Chemother
January 2022
ViiV Healthcare, Research Triangle Park, North Carolina, USA.
Antimicrob Agents Chemother
May 2023
Gilead Sciences, Inc. Foster City, CA, USA.
The HIV integrase (IN) strand transfer inhibitor (INSTI) bictegravir (BIC) has a long dissociation half-life (t) from wild-type IN-DNA complexes: BIC 163 hr > dolutegravir (DTG) 96 hr > raltegravir (RAL) 10 hr > elvitegravir (EVG) 3.3 hr. In cells, BIC had more durable antiviral activity against wild-type HIV after drug washout than RAL or EVG.
View Article and Find Full Text PDFAIDS
March 2019
Department of Molecular Microbiology and Immunology.
: The oligomerization of HIV-1 integrase onto DNA is not well understood. Here we show that HIV-1 integrase binds the DNA in biphasic (high-affinity and low-affinity) modes. For HIV-1 subtype B, the high-affinity mode is ∼100-fold greater than the low-affinity mode (Kd.
View Article and Find Full Text PDFSci Rep
October 2017
Laboratory of Biology and Applied Pharmacology (LBPA), CNRS UMR8113, IDA FR3242, ENS Paris-Saclay, Université Paris-Saclay, F-94235, Cachan, France.
FDA-approved integrase strand transfer inhibitors (raltegravir, elvitegravir and dolutegravir) efficiently inhibit HIV-1 replication. Here, we present fluorescence properties of these inhibitors. Dolutegravir displays an excitation mode particularly dependent on Mg chelation, allowing to directly probe its Mg-dependent binding to the prototype foamy virus (PFV) integrase.
View Article and Find Full Text PDFNature
February 2016
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Integration of the reverse-transcribed viral DNA into the host genome is an essential step in the life cycle of retroviruses. Retrovirus integrase catalyses insertions of both ends of the linear viral DNA into a host chromosome. Integrase from HIV-1 and closely related retroviruses share the three-domain organization, consisting of a catalytic core domain flanked by amino- and carboxy-terminal domains essential for the concerted integration reaction.
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