Strain-specific effect on biphasic DNA binding by HIV-1 integrase. (1st March 2019)

• Record Type: Journal Article
• Authors: Hill, Kyle J.; Rogers, Leonard C.; Njenda, Duncan T.; Burke, Donald H.; Sarafianos, Stefan G.; Sönnerborg, Anders; Neogi, Ujjwal; Singh, Kamalendra
• Is Part Of: AIDS. Volume 33:Number 3(2019)
• Publication Date: 2019-03-01
• Subjects: AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000002078
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : N/A: 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 ( K d .DNA = 37 and 3400 nmol/l, respectively). The K d .DNA values of patient-derived integrases containing subtype-specific polymorphisms 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.