Background:  The current distribution of retroviruses among human and non-human primate species reflects substantial co-evolution between the host and the infectious agent. Adaptation of the virus to pressure exerted by the immune system and other host cell barriers (such as innate cellular defenses), will affect the evolution of both host and viral genomes. Evolutionary analysis may serve as a useful tool to identify the host and viral proteins involved in genetic conflicts. The present study assesses global adaptation between primates and simian immunodeficiency virus (SIV), and uses 4 model host proteins to better define patterns of adaptive evolution.

Methods:  Congruence of host and virus phylogeny was tested as follows. First a phylogenetic tree was reconstructed based on all available full-length genomes from SIV isolates using MEGA3.1. These were then matched to the phylogenetic tree of human and non-human primates. Patterns of substitutional evolution were assessed for TRIM5, TRIM19/PML, PPIA, and APOBEC3G using DNA from humans, great apes, gibbons, and Old and New World monkeys. All selection analyses, including the analysis of positive selection in the cellular defense genes were performed by the PAML (phylogenetic analysis by maximum likelihood) program package.

Results:  Matching of primate and SIV/HIV phylogenetic trees indicate that host–virus co-evolution precisely predicts the phylogeny of SIV isolates. Detailed analysis of the 4 model proteins confirmed the previously described pattern of strong positive selection on TRIM5 and multiple regions of conflict. It also identified strong positive selection on APOBEC3G with better defined regions of host gene–virus co-evolution than previously reported, strong purifying selection for TRIM19/PML with absence of residues under positive selection, and full conservation of PPIA among primates.

Conclusions:  Comparative phylogenetic analysis underscores the extent of co-evolution of the primate hosts and their SIV species. In contrast to TRIM5 and APOBEC3G, evolutionary analysis at the protein level suggests that PPIA (incorporated into HIV-1) is not under differential pressure in primates. The strong conservation of the TRIM19/PML protein sequences among primates suggests that this gene does not play a role in antiretroviral defense.