Mutational analysis of the 5' leader region of simian foamy virus type 1

The sequence within the 5' untranslated region of the retroviral genome contains important cis elements for many steps in viral replication. There is limited information available on the role of this region in foamy virus replication. Similar to other retroviruses, the 5' untranslated region of foamy viruses predicts extensive RNA secondary structure. Serial mutations that could change parts of the predicted secondary structure were introduced in the 5' leader sequence including the R-U5 region of simian foamy virus type 1 (SFV-1) to investigate their role in virus genome packaging and virus replication. Point mutations in the R-U5 regions at nucleotide positions 7-12 (I), 241-243 (B), and 256-257 (D) had no effect on virus replication. Base substitution mutation at positions 193-195 (C), however, severely impaired virus replication. Deletion of sequences in the leader region, between the primer-binding site and the gag gene, at positions 364-399 (d1), 397-435 (d2), or 364-435 (d3), which included sequences for RNA genome dimerization, also blocked SFV-1 replication. Interestingly, none of these mutations affected genome packaging or the synthesis of viral transcripts, suggesting that a step(s) of virus replication following packaging is affected. The region between the primer-binding site and the gag gene, therefore, is not essential for foamy virus genome packaging. Furthermore, the cis-acting elements for genome dimerization and packaging appear to be localized in separate regions for foamy viruses.