Comparative biochemical analysis of HIV-1 subtype B and C integrase enzymes.
BACKGROUND
Integrase inhibitors are currently being incorporated into highly active antiretroviral therapy (HAART). Due to high HIV variability, integrase inhibitor efficacy must be evaluated against a range of integrase enzymes from different subtypes.


METHODS
This study compares the enzymatic activities of HIV-1 integrase from subtypes B and C as well as susceptibility to various integrase inhibitors in vitro. The catalytic activities of both enzymes were analyzed in regard to each of 3' processing and strand transfer activities both in the presence and absence of the integrase inhibitors raltegravir (RAL), elvitegravir (EVG), and MK-2048.


RESULTS
Our results show that integrase function is similar with enzymes of either subtype and that the various integrase strand transfer inhibitors (INSTIs) that were employed possessed similar inhibitory activity against both enzymes.


CONCLUSIONS
This suggests that the use of integrase inhibitors against HIV-1 subtype C will result in comparable outcomes to those obtained against subtype B infections.
Bar-Magen
Tamara
T
McGill University AIDS Centre, Lady Davis Institute-Jewish General Hospital, Montreal, Quebec, Canada. tamara.bar-magen@mail.mcgill.ca
Sloan
Richard D
RD
Faltenbacher
Verena H
VH
Donahue
Daniel A
DA
Kuhl
Björn D
BD
Oliveira
Maureen
M
Xu
Hongtao
H
Wainberg
Mark A
MA
D004279:DNA, Viral / Q000378:metabolism; D005838:Genotype; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000145:classification / Q000201:enzymology* / Q000235:genetics; D020128:Inhibitory Concentration 50; D011760:Pyrrolidinones / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D000068898:Raltegravir Potassium
D004279:DNA, Viral; D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D015363:Quinolones; D000068898:Raltegravir Potassium; C509700:elvitegravir; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1