MHC Class I-like Gene in Squirrel Monkey Cytomegalovirus and the Evolution of the Virus

Homology searches between viral and human peptides revealed that the S9 protein of squirrel monkey cytomegalovirus (Saimiriine herpesvirus 4 strain [SBHV4]) shares 60.6% amino acid identity across 86.3% of full-length human HLA-A. This represents the most extensive and highest degree of homology reported to date between a viral protein and an MHC class I molecule. Phylogenetic analysis of MHC class I-like DNA sequences from primate HLA-A orthologs and SBHV4-S9 gene suggested that SBHV4-S9 was likely acquired via LINE-1-mediated horizontal gene transfer from the African Old World monkey Piliocolobus tephrosceles or a close ancestor 1.63-6.02 million years ago. SBHV4-S9 appeared to have undergone purifying selection following divergence from P. tephrosceles. Furthermore, phylogenetic analysis of the SBHV4-S1 gene and primate SLAMF6-like genes suggested that this gene was acquired after divergence from a close ancestor of the New World monkeys Saimiri oerstedii and Saimiri sciureus. Comprehensive evaluation of the similarity between eight SBHV4 genes (including S1 and S9) and their respective homologs in 241 primate species, assessed via PCA-syncmer-based Wasserstein distances, revealed that the overall relatedness between SBHV4 and African Cercopithecus ascanius, Cercopithecus pogonias, and Allenopithecus nigroviridis, respectively was significantly greater (i.e., exhibited shorter Wasserstein distances) in each case than that observed with all examined members of the genus Saimiri and Piliocolobus tephrosceles. Collectively, these findings indicate that SBHV4, although isolated from Saimiri sciureus in South America, appears to have a historical connection with Old World monkeys in Africa, despite the typically high host specificity of cytomegaloviruses.