Predictive analysis of binding affinity among human cytomegalovirus (HCMV) proteins and class-I major histocompatibility complex (MHC-I) molecules

• Author Details:   
• Balaka Biswas
• Ankita Bhaduri
• Mousumi Saha
• Dipanwita Das
• Agniswar Sarkar ^*

---

View PDF

Background: Human Cytomegalovirus (HCMV) is a widespread herpesvirus that establishes persistent infections by evading host immune surveillance. A critical strategy involves the disruption of antigen presentation via Class I Major Histocompatibility Complex (MHC-I) molecules, thereby impairing cytotoxic T lymphocyte (CTL) recognition. This immune evasion is facilitated by a group of HCMV-encoded glycoproteins, US2, US3, US6, US10, and US11, which target distinct stages of the MHC-I processing and presentation pathway.

Materials and Methods: A comprehensive bioinformatics workflow was employed to characterize the structure and function of key HCMV proteins. Protein sequences were sourced from NCBI, and domain structures were analyzed using the Conserved Domain Database (CDD). Coding potential was assessed through reverse translation and ORF prediction. Structural modelling and homology were evaluated via Phyre2, PSI-BLAST, and Clustal Omega. Physicochemical properties were determined using ExPASy ProtParam, and transmembrane regions were predicted with TMHMM. Model validation involved RCSB-PDB, PDBsum, Ramachandran plots, and TM-align. Protein-MHC interactions were visualized using Discovery Studio and PyMOL.

Results: US2 and US3 mimic MHC-I structures to bind and retain them within the endoplasmic reticulum, while US6 inhibits TAP-mediated peptide translocation. US10, with its dual transmembrane topology, disrupts HLA-G trafficking, impacting both CTL and NK cell responses.

Conclusion: This study demonstrates how HCMV proteins interfere with MHC-I antigen presentation, emphasizing their roles in immune evasion. US10 emerges as a key therapeutic target. The findings offer novel insights into HCMV’s molecular strategies, paving the way for the development of targeted antiviral treatments and vaccine design.