Association of Ribosomal Proteins with Epstein-Barr Virus Proteins in Nasopharyngeal Carcinoma
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Universiti Malaysia Sarawak
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Epstein-Barr virus (EBV) latent infection plays a crucial role in nasopharyngeal carcinoma (NPC). Association of EBV-encoded latent gene products with host ribosomal proteins (RPs), thus far, have remained under-explored, despite implications indicating the involvement of RPs in the aetiology of several human cancers. The quest to elucidate the intricate interactions between EBV proteins and RPs in the present study was facilitated by implementing a computational approach, which provided integral conceptual insight into the interplay among the host and virus. The in silico structural similarity-based strategy enabled the prediction of 48 potential interactions between 26 RPs and the EBV proteins EBNA1, LMP1, LMP2A, LMP2B and BARF1. Gene ontology analysis of the putative protein-protein interactions (PPIs) revealed their probable involvement in RNA binding, ribosome biogenesis, metabolic process, biosynthetic process and gene expression. Pathway analysis uncovered their participation in viral infection strategies (such as viral transcription), as well as NPC oncogenesis (such as Wnt signaling and EGFR signaling pathways). The ensuing molecular docking procedure, furthermore demonstrated the functional viability of the predicted interactions (EBNAI- RPeS I0, EBNA I -RPeS25, EBNA I -RPuL I O and EBNA 1-RPuL 11), in terms of interaction energies and the interfacial residues involved in these associations. Lastly, the qualitative in vitro RT-PCR technique employed to recognize the presence of ribosomal protein genes RPeSIO, RPeS25, RPuL10 and RPuLII in the NPC cell line C666-1, enabled the detection of the aforesaid targeted genes. As a result, the cross-disciplinary strategy executed in the current study systematically expedited the identification of functionally relevant (le noi'o interactions. It is anticipated that the predicted PPIs could facilitate the selection of potential targets for further experimental studies, which ultimately would enhance our understanding of the relationship between ribosomal proteins, EBV infection and NPC tumourigenesis.