A role for DNA-PK in retroviral DNA integration

Retroviral DNA integration is catalyzed by the viral protein integrase. Her e, it is shown that DNA-dependent protein kinase (DNA-PK), a host cell prot ein, also participates in the reaction. DNA-PK-deficient murine scid cells infected with three different retroviruses showed a substantial reduction i n retroviral DNA integration and died by apoptosis. Scid cell killing was n ot observed after infection with an integrase-defective virus. suggesting t hat abortive integration is the trigger for death in these DNA repair-defic ient cells. These results suggest that the initial events in retroviral int egration are detected as DNA damage by the host cell and that completion of ;the integration process requires the DNA-PK-mediated repair pathway.