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 replic ation the activity of a transcriptional trans-activator (Tas) as well as Ta s-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 U 3 promoter of the CFV long terminal repeat was substituted by the constitut ively active human cytomegalovirus immediate early gene enhancer/promoter w as constructed. This plasmid (pTS12) and a derivative (pTS13), which has a deletion in the tas gene, gave rise to replication-competent virus. Compare d with parental CFV, both mutants replicated only very poorly, with retarde d growth kinetics and maximal cell-free virus titres reduced by approximate ly three orders of magnitude. Mutation of the DD35E motif of the CFV integr ase 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 in to a simple one by incorporation of a constitutively active promoter from a nother virus which regularly does not integrate into the host cell genome.