Study of human foamy virus proviral integration in chronically infected murine cells

This report describes integration sites of human foamy virus (HFV) in chronically infected BALB/c murine cells that we isolated by inverse PCR and characterized. We show that integration of HFV proviral genome mainly occurs in highly repetitive and/or transcriptionally active regions and leads to the formation of a 4-bp cellular direct repeat sequence at each provirus extremity. As non-random deletions were previously described in the HFV be/1 transactivator gene as well as in the long terminal repeats (LTRs), these regions were verified in integrated HFV. The analysis reveals that, in the studied chronic state, the defective interfering virus (delta HFV) is the main integrated proviral form and is always associated with a small LTR. Our results show that HFV can use a classic retroviral integration process to enter the host cell genome and stress the importance of delta HFV and the short LTRs in the establishment of the chronic state of infection.