Human genes with relative synonymous codon usage analogous to that of polyomaviruses are involved in the mechanism of polyomavirus nephropathy.

Abstract

Human polyomaviruses (HPyVs) can cause serious and deleterious infections in human. Yet, the molecular mechanism underlying these infections, particularly in polyomavirus nephropathy (PVAN), is not well-defined. In the present study, we aimed to identify human genes with codon usage bias (CUB) similar to that of HPyV genes and explore their potential involvement in the pathogenesis of PVAN. The relative synonymous codon usage (RSCU) values of genes of HPyVs and those of human genes were computed and used for Pearson correlation analysis. The involvement of the identified correlation genes in PVAN was analyzed by validating their differential expression in publicly available transcriptomics data. Functional enrichment was performed to uncover the role of sets of genes. The RSCU analysis indicated that the A- and T-ending codons are preferentially used in HPyV genes. In total, 5400 human genes were correlated to the HPyV genes. The protein-protein interaction (PPI) network indicated strong interactions between these proteins. Gene expression analysis indicated that 229 of these genes were consistently and differentially expressed between normal kidney tissues and kidney tissues from PVAN patients. Functional enrichment analysis indicated that these genes were involved in biological processes related to transcription and in pathways related to protein ubiquitination pathway, apoptosis, cellular response to stress, inflammation and immune system. The identified genes may serve as diagnostic biomarkers and potential therapeutic targets for HPyV associated diseases, especially PVAN.