Abstract
Virus-host interactions have contributed to the acquisition of host-derived genetic material by viral genomes, although the mechanisms underlying such events remain incompletely understood. Here, we identified the S9 protein of squirrel monkey cytomegalovirus (Saimiriine herpesvirus 4; SBHV4) as a unique viral protein showing extensive similarity to mammalian major histocompatibility complex class I (MHC class I) molecules. SBHV4-S9 shared 60.6% amino acid identity across 86.3% of the full-length human HLA-A protein, representing the highest level of similarity between a viral protein and an MHC class I molecule identified in Virus-Host DB-based screening. Structural modeling demonstrated that SBHV4-S9 possesses an overall architecture highly similar to HLA-A, including the characteristic MHC class I domains. Comprehensive phylogenetic analyses of primate MHC class I-like genes, incorporating assessments of substitution saturation, potential recombination signals, and comparisons between complete sequences and non-peptide-binding regions, showed that SBHV4-S9 consistently clustered with Old World monkey MHC class I sequences, including those from the genus Cercopithecus. However, the complex evolutionary history of MHC class I genes prevented definitive identification of the donor lineage or acquisition mechanism. These findings identify SBHV4-S9 as an exceptional viral MHC class I-like protein and highlight the complexity of reconstructing ancient virus-host evolutionary events.
Acknowledgements
This work was partially supported by Grants-in-Aid for Scientific Research from the JSPS (24K21913 to E.H.). Computations were performed on the NIG supercomputer at ROIS National Institute of Genetics, Japan.
Funding
This work was partially supported by Grants-in-Aid for Scientific Research from the JSPS (24K21913 to E.H.).
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Hondo, E., Mizutani, T., Shimoda, H. et al. An exceptional viral MHC class I-like protein encoded by squirrel monkey cytomegalovirus. Sci Rep (2026). https://doi.org/10.1038/s41598-026-68632-1
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DOI: https://doi.org/10.1038/s41598-026-68632-1