Journal of Health & Medical Informatics

Characterization of Molecular Mimicry Between UL18 Glycoprotein of Human Cytomegalovirus [HCMV] and Class-I MHC Molecule through Pattern-based Analysis: An In-silico Approach

Abstract

Sarkar A, Chatterjee A, Ansari S and Chakraborty N

Viral replication occurs using the host cell synthesis mechanisms and they are able to exploit the mechanisms of nucleic acid replication and protein translation machinery. Viral proteins require a target to fit subcellular compartments of the host cell and localized in different cellular compartments including the nucleus. Human Cytomegalovirus downregulates expression of traditional class-I MHC [Major Histocompatibility Complex] molecules at the infected cell surface and allows the infected cells to avoid acknowledgment by cytotoxic T-cells. In the present study, we have focused on generally accessible online and offline computational tools to examine practical and fundamental characteristics of the most conserved domain [CD] of UL18 gene along with the viral class-I MHC molecule. Six open reading frames [ORF] were reanalyzed by selecting start codon. Site-specific homology was determined to the MHC class-I molecule [19 to 197 residual position; ID: pfam00129, E-value: 3.26e-14]. The predicted protein architecture contained about 28.90% helices [107 residues] and 10.32% strands [38 residues]. The tertiary structure represented that 276 residues [75% of sequence] were modeled by the single highest scoring template with 100% confidence and the structure represents a peptide-binding viral MHC mimic, apprenticed to a host inhibitory receptor [pdb code-3d2u]. Thus, our analysis suggests that the homologous sequence corresponding to MHC class-I gene is situated between 19 and 200th residues of UL18 ORF and the recognition domain was identified with significant E-value. Our study also demonstrated that the ORF18 is homologous to the Ig-superfamily in 229-289th position. Therefore, these domains were found to date homologous in HCMV proteins suggesting a particular functional role during infection. In light of the above, further experimental steps are needed to elucidate the exact role of the UL18 during infections.