The human foamy virus internal promoter directs the expression of the functional Bel 1 transactivator and Bet protein early after infection.

The human foamy virus or spumaretrovirus (HFV) is a complex retrovirus that has the capacity to code not only for the three retroviral genes gag, pol, and env but, in addition, for at least three bel genes. The HFV provirus contains two different and functionally active promoters: the classical retroviral promoter in the 5' long terminal repeat and a recently identified second promoter in the env gene upstream of the bel genes. Both promoter/enhancers are strongly dependent on the HFV transcriptional transactivator protein Bel 1. Here we report that the internal promoter directs the synthesis of viral transcripts that code for functionally active Bel 1 and for Bet proteins that appeared early after HFV infection. The viral mRNAs of the internal promoter have a 112-nucleotide-long leader exon and were spliced predominantly at the first splice donor site in the 5' untranslated region. The data were obtained by transient expression assays, transactivation experiments, and RNA analyses of transcripts derived from HFV-infected cells. The results provide strong evidence for the crucial role the internal promoter plays during HFV infection in generating bel-specific transcripts.