Cell context-dependent involvement of ATR in early stages of retroviral replication

Retroviral DNA integration leaves behind a single-strand DNA discontinuity at each virus:host DNA junction. It has long been proposed that cellular proteins detect and repair the integrated DNA and that failure to do so might lead to apoptotic cell death, but their identity remains unknown. PIKK family members ATM, DNA-PKcs and ATR have all been proposed to be important for HIV-1 replication, but these findings turned out to be very controversial. In order to clarify their role in retroviral replication, we analyzed the effect of pharmacological inhibitors and of a dominant-negative version of ATR on the replication of retroviruses in cell lines relevant to HIV-1 infection. Our data show that ATR and probably other PIKKs as well are involved in retroviral replication in some but not all cell lines and that ATR increases the frequency of retroviral transduction by a mechanism other than the enhancement of infected cell survival.