Researchers have been using network biology for designing novel antiviral drug therapies 16. Viruses tend to regulate host biological processes by manipulating its cell proteome. Protein interaction network provides a plethora of information when it comes to virus-host relationship because viruses entirely depend upon the host factors for their survival 14, 15. E8 ∧E2, a transcript, is created by the fusion of E8 with carboxy terminal of E2 12, and E1 ∧E4 is generated by the fusion of E1 to the Open Reading Frame (ORF) of E4 13. Besides these 8 proteins, there are a few other macromolecules found in literature which are actually the transcripts made by the fusion of two existing HPV proteins. The HPV genome encodes 8 proteins among which 2 are structural viral capsid proteins (L1 and L2) while 6 are non-structural viral proteins (E1, E2, E4, E5, E6, E7) 10, 11. HPV is a small ~8 kb in size, non-enveloped circular dsDNA virus 5, 10. HPV is a serious threat to human life and it is causing 250,000 deaths annually, among which 85% of cases are occurring in low and middle-income countries 9. The most talked about high-risk HPV strains are HPV 6, 11, 16, 18, 31, 33, 35, 45, 52 and 58 with type 16 and 18 responsible for 70% of cervical cancer cases 6, 7, 8. According to World Health Organization (WHO) current factsheets, there are more than 100 genotypes of HPV, out of which 14 strains are high-risk. Among these cancers, cervical cancer ranks 4th in affecting women worldwide 4 while in developing countries it ranks second 5. Human papilloma virus (HPV) is associated with approximately 5% of all human cancers affecting 0.6 million people worldwide with cervical, anal, oropharyngeal, penile and vulvovaginal cancers 1, 2, 3. It can be concluded that the molecules found in this study could be potential targets and could be used by scientists in their drug design studies. We found out a group of genes which is not targeted by the existing drugs available for HPV infections. Among the viral proteins, E7 has the highest number of associations in the network followed by E6, E2 and E5. The functional enrichment analysis of these top-notch key genes is performed using KEGG pathway and Gene Ontology analysis, which reveals that the gene set is enriched in cell cycle a crucial cellular process, and the second most important pathway in which the gene set is involved is viral carcinogenesis. We found out 2988 interactions between 12 HPV and 2061 human proteins among which we identified MYLK, CDK7, CDK1, CDK2, JAK1 and 6 other human proteins associated with multiple viral oncoproteins. In current study, we construct an integrated protein interaction map of HPV with its host human in Cytoscape and analyze it further by using various bioinformatics tools. Study on protein interaction maps of pathogens with their host is a recent trend in ‘omics’ era and has been practiced by researchers to find novel drug targets. Human papilloma virus (HPV) is a serious threat to human life globally with over 100 genotypes including cancer causing high risk HPVs.
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