Construction and in vitro characterization of attenuated feline immunodeficiency virus long terminal repeat mutant viruses

AP-1- and ATF-binding sites are cis-acting transcriptional elements within the U3 domain of the feline immunodeficiency virus (FIV) long terminal repe at (LTR) that serve as targets for cellular activation pathways and may reg ulate virus replication. We report that FIV LTR mutant proviruses encoding U3 deletions of the ATF-binding sequence exhibited restricted virus express ion and replication in both feline lymphocytes and macrophages. In contrast , deletion of the AP-1 site had negligible effects on virus expression and replication. FIV LTR mutant proviruses encoding deletions of both the AP-1 and ATF sites or a 72-bp deletion encompassing the AP-1 site, duplicated C/ EBP sites, and ATF sites were severely restricted for virus expression. The se results demonstrate that deletion of either the ATF-binding site or mult iple cis acting transcriptional elements attenuates FIV. These attenuated F IV mutants provide opportunities to characterize the role of cis-acting ele ments in virus replication in vice and to test LTR mutants as attenuated vi rus vaccines.