Lentiviral vectors pseudotyped with the vesicular stomatitis virus G glycoprotein or Lassa virus glycoprotein enter the cell via receptor-mediated uptake into clathrin-coated vesicles. Rapamycin treatment does not alter virus binding or abundance of the cognate receptors, but selectively enhances release of vector particles into the cytoplasm. Due to the increased abundance of vector particles in the cytoplasm, the subsequent steps of reverse transcription and integration into the host cell genome are enhanced.