Replication of a foamy virus mutant with a constitutively active U3 promoter and deleted accessory genes

Foamy viruses (FVs) are complex retroviruses which require for their replication the activity of a transcriptional trans-activator (Tas) as well as Tas-responsive elements in the viral promoters. A mutant of the chimpanzee FV strain, CFV/hu (previously called human FV), genome in which most of the U3 promoter of the CFV long terminal repeat was substituted by the constitutively active human cytomegalovirus immediate early gene enhancer/promoter was constructed. This plasmid (pTS12) and a derivative (pTS13), which has a deletion in the tas gene, gave rise to replication-competent virus. Compared with parental CFV, both mutants replicated only very poorly, with retarded growth kinetics and maximal cell-free virus titres reduced by approximately three orders of magnitude. Mutation of the DD35E motif of the CFV integrase to DA35E rendered the recombinant TS virus replication-deficient. This indicated that provirus integration is probably still required for this FV derivative, which had been converted from a complex regulated retrovirus into a simple one by incorporation of a constitutively active promoter from another virus which regularly does not integrate into the host cell genome.