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

This report describes integration sites of human foamy virus (HFV) in chron ically infected BALB/c murine cells that we isolated by inverse PCR and cha racterized. We show that integration of HFV proviral genome mainly occurs i n highly repetitive and/or transcriptionally active regions and leads to th e formation of a 4-bp cellular direct repeat sequence at each provirus extr emity. As non-random deletions were previously described in the HFV bell tr ansactivator gene as well as in the long terminal repeats (LTRs), these reg ions were verified in integrated HFV. The analysis reveals that, in the stu died chronic state, the defective interfering virus (Delta HFV) is the main integrated proviral form and is always associated with a small LTR. Our re sults show that HFV can use a classic retroviral integration process to ent er the host cell genome and stress the importance of Delta HFV and the shor t LTRs in the establishment of the chronic state of infection.