Evolution of the long terminal repeat and accessory genes of feline immunodeficiency virus genomes from naturally infected cougars.

FIVpco is a member of the feline immunodeficiency virus family that is endemic in wild cougar populations. Virus replication is robust in FIVpco-infected cougars but there are no consequences of infection to cougar survival, fecundity or susceptibility to other infections. Unlike pathogenic lentiviruses, there is no evidence for positive selection on FIVpco gag or env. To better understand how lentivirus genomes evolve in natural infections, we evaluated the regulatory region and accessory genes from fourteen full-length FIVpco genomes, which represent the FIVpco diversity in the Northern Rockies Ecosystem. Our data demonstrate that the two sister groups of FIVpco have each acquired binding sites for different interferon response factors (IRF). The most variable gene in the FIVpco genome encodes OrfA, although there is no indication that it, or any other accessory gene, is under positive selection. There is a single-splice acceptor site for vif expression, which is conserved among all FIVpco genomes. However, there are several putative means to express rev and orfA, which differ between the phylogenetic groups of FIVpco. Our comparative study on divergent FIVpco genomes indicates that variation in potential gene regulation mechanisms, not changes in structural proteins, characterize the evolution of FIVpco in natural infections.