Long terminal repeat U3 length polymorphism of human foamy virus

Size determination of the long terminal repeat (LTR) of an early (1985) and a more recent (1993) passage of wild-type human foamy virus (HFV) revealed that the virus has undergone substantial deletions in the U3 region upon replication in tissue culture. Two LTR deletion variants (HSRV1 and 2) have been characterized in the past and used to construct molecular clones which are replication competent in cell culture. We now report the molecular cloning, sequencing, and biological characterization of an HFV genome with full-length LTR (pHFV2). Sequence analysis revealed that the deletions in HSRV1 and 2 are nonrandom and probably occurred by misalignment during reverse transcription. The comparative analysis of HFV2 and the variant with the largest U3 deletion, HSRV2, revealed a differential ability to replicate in human cell cultures. While HSRV2 replicated faster in diploid human fibroblasts, cells which have been used extensively for amplification of HFV in the past, replication of HFV2 was faster in a lymphoblastoid cell line. Reporter gene assays indicated that the cell-type specific ability of the LTRs to respond to the viral transcriptional transactivator may be a likely, reason for the different growth properties of both viruses and for the occurrence of the HFV U3 deletions. In foamy virus-infected chimpanzees only the full-length type of LTR was observed; however, the HSRV1 deletion variant was detected as the dominating virus in an accidentally HFV-infected human.