Computer aided epitope prediction for glycoprotein-B in human cytomegalovirus

Introduction Human cytomegaloviruss (HCMV), a ubiquitous, opportunistic pathogen, is a member of the Herpesviridae family of viruses and is alternatively known as human herpesvirus-5 (HHV-5). [1] Following infection, the virus resides in endothelial cells, macrophages, or granulocyte stem cells [2] and may cause reinfection if the host is rendered immunosuppressed. Primary HCMV infection of persons with intact immune systems often results in a self-limiting asymptomatic disease, while HCMV is a significant human pathogen for immunocompromised individuals that is often manifested as severe and debilitating sequelae. [3] Clinically significant CMV disease frequently develops in patients immunocompromised by HIV, solid-organ transplantation, and bone-marrow transplantation. Additionally, congenital transmission from a mother with acute infection during pregnancy is a significant cause of neurological abnormalities and deafness in newborns. Symptomatic disease in immunocompromised individuals can affect almost every organ of the body, resulting in fever of unknown origin, pneumonia, hepatitis, encephalitis, myelitis, colitis, uveitis, retinitis, and neuropathy. [4] Infection of immunocompetent persons has had limited consequences in the vast majority of cases, indicating the importance of a functional immune response in the control of HCMV infections. [5] Glycoprotein B (gB) is the most abundant constituent of the viral envelope and is a potent immunogenic HCMV protein. [6, 7] gB plays key roles in the process of CMV entry into host cells. This process is a multistep cascade beginning with attachment of the virus to the cell surface and ending with fusion of the virus envelope with the cell plasma membrane. Attachment of CMV to host cells is mediated by an initial interaction between viral gB and/or gM and cell surface heparan sulphate proteoglycans. [8] The antibody binding sites on gB have been studied by several laboratories, and both conformationally dependent and linear binding sites have been described. [9] Extensive strainspecific virus neutralization has been observed in the vast majority of studies that have employed against gB and gH in the neutralization of different clinical HCMV isolates, and some of the B-cell epitopes involved have been characterized. [10, 11, 12, 13] The aim of present work was to predict the T-cell and B-cell epitopes for envelope glycoprotein B (gB) of the human cytomegalovirus (strain AD169) and to perform the comparative docking study of all predicted epitopes (small peptides) with their respective receptors. Materials and Methods Tools used ProPred 1 Server: ProPred 1 is an on-line web tool for the prediction of peptide binding to MHC class-I alleles (http://www.imtech.res.in/raghava/propred1/) . This is a matrixbased method that allows the prediction of MHC binding sites in an antigenic sequence for 47 MHC class-I alleles. The server represents MHC binding regions within an antigenic sequence in user-friendly formats. [14] MHC2Pred Server: The MHC2Pred is an SVM based method for prediction of promiscuous MHC class II binding peptides (http://www.imtech.res.in/raghava/mhc2pred/). The data for training has been extracted from MHCBN and JenPep database. All the peptides having IC50 value less than 500nm has been considered as binders and peptides with IC50 value greater than 500nm are considered as non-binders. The binders and non-binders for all alleles have been obtained from MHCBN and JenPep database. For the development of MHC binder prediction method, an elegant machine learning technique SVM has been used. [15]