Integrase is the key enzyme that mediates integration of retroviral DNA into
cellular DNA which is essential for viral replication. Inhibitors of HIV-1 that
target integrase recognize the nucleoprotein complexes formed by integrase and
viral DNA substrate (intasomes) rather than the free enzyme. Atomic resolution
structures of HIV-1 intasomes are therefore required to understand the
mechanisms of inhibition and drug resistance. To date, prototype foamy virus
(PFV) is the only retrovirus for which such structures have been determined. We
show that PFV strand transfer complexes (STC) can be assembled on product DNA
without going through the normal forward reaction pathway. The finding that a
retroviral STC can be assembled in this way may provide a powerful tool to
alleviate the obstacles that impede structural studies of nucleoprotein
intermediates in HIV-1 DNA integration.
