Strain-specific Effect on Biphasic DNA Binding by HIV-1 Integrase

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 similar to 100-fold greater than the low-affinity mode (K-d.DNA = 37 and 3400 nmol/l, respectively). The K-d.DNA values of patient-derived integrases containing subtype-specific polymor-phisms were affected two-to four-fold, suggesting that polymorphisms may have an influence on effective-concentrations of inhibitors, as these inhibitors preferably bind to integrase-DNA complex.