LEDGINs inhibit late stage HIV-1 replication by modulating integrase multimerization in the virions.

ABSTRACT:

Background

LEDGINs are novel allosteric HIV integrase (IN) inhibitors that target the lens epithelium-derived growth factor (LEDGF)/p75 binding pocket of IN. They block HIV-1 integration by abrogating the interaction between LEDGF/p75 and IN as well as by allosterically inhibiting the catalytic activity of IN.

Results

Here we demonstrate that LEDGINs reduce the replication capacity of HIV particles produced in their presence. We systematically studied the molecular basis of this late effect of LEDGINs and demonstrate that HIV virions produced in their presence display a severe replication defect. Both the late effect and the previously described, early effect on integration contribute to LEDGIN antiviral activity as shown by time-of-addition, qPCR and infectivity assays. The

SUBMITTER: Desimmie BA 

PROVIDER: S-EPMC3671127 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature