LEDGF/p75 is critical but not essential for multiple-round HIV 1 replication

Background Via its interaction with the cellular cofactor LEDGF/p75, HIV-1 integration is targeted towards active genes. Several strategies were used to show the important role of LEDGF/p75 in viral replication. After RNAi-mediated knockdown of LEDGF/p75, residual replication was observed, possibly supported by minute LEDGF/p75 protein levels. Mouse knockout fibroblasts were generated, enabling analysis of high-titer, single-round lentiviral vector transduction, but not multiple-round replication. To enable evaluation of multiple-round replication in the complete absence of LEDGF/p75, a human LEDGF/p75 knockout cell line was generated (-/-), leaving the p52 splice variant intact.