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

Homology searches between the entire viral peptides and the human peptides revealed a squirrel monkey cytomegalovirus (Saimiriine herpesvirus 4 strain [SBHV4]) S9 protein exhibiting 60.6% amino acid sequence identity across 86.3% of the full-length human HLA-A. This represents the most extensive and highest level of homology observed to date between a viral protein and an Major Histocompatibility Complex (MHC) class I molecule. Molecular modeling of the S9 and HLA-A proteins and subsequent structural comparison confirmed significant similarity, including the antigen-presenting region. Although cytomegalovirus exhibits high host specificity, the presence of the S9 protein in this virus warrants immunological caution in the event of cross-species transmission. Phylogenetic analysis of MHC class I-like gene sequences corresponding to primate HLA-A and SBHV4 suggested that SBHV4-S9 was likely acquired via LINE-1-mediated horizontal gene transfer from the African Old World monkey Papio anubis or a closely related ancestral species approximately 12.9 to 22.2 million years ago. SBHV4-S9 displayed evidence of strong negative selection following its divergence from Papio anubis. Furthermore, phylogenetic analysis of the SBHV4-S1 gene and primate SLAMF6-like genes indicated that this gene was acquired after the divergence from the New World monkey Saimiri boliviensis boliviensis. Evaluation of the overall genetic similarity between the SBHV4 genome and cDNAs from individual primate species using hierarchical clustering based on Levenshtein distance and Wasserstein distance revealed a higher degree of similarity between the SBHV4 genome and Papio anubis cDNA compared to that with Saimiri boliviensis boliviensis cDNA. Taken together, these findings suggest that Papio anubis has a longer co-evolutionary history with SBHV4 than squirrel monkeys, and that SBHV4 likely spread from Africa to South America, acquiring novel genomic elements in new hosts.