Abstract
BackgroundHepatitis C Virus is becoming a major health problem in Asia and across the globe since it is causing serious liver diseases including liver cirrhosis, chronic hepatitis and hepatocarcinoma (HCC). Protein interaction networks presents us innumerable novel insights into functional constitution of proteome and helps us finding potential candidates for targeting the drugs.MethodsHere we present a comprehensive protein interaction network of Hepatitis C Virus with its host, constructed by literature curated interactions. The network was constructed and explored using Cytoscape and the results were further analyzed using KEGG pathway, Gene Ontology enrichment analysis and MCODE.ResultsWe found 1325 interactions between 12 HCV proteins and 940 human genes, among which 21 were intraviral and 1304 were HCV-Human. By analyzing the network, we found potential human gene list with their number of interactions with HCV proteins. ANXA2 and NR4A1 were interacting with 6 HCV proteins while we found 11 human genes which were interacting with 5 HCV proteins. Furthermore, the enrichment analysis and Gene Ontology of the top genes to find the pathways and the biological processes enriched with those genes. Among the viral proteins, NS3 was interacting with most number of interactors followed by NS5A and so on. KEGG pathway analysis of three set of most HCV- associated human genes was performed to find out which gene products are involved in certain disease pathways. Top 5, 10 and 20 human genes with most interactions were analyzed which revealed some striking results among which the top 10 host genes came up to be significant because they were more related to Influenza A viral infection previously. This insight provides us with a clue that the set of genes are highly enriched in HCV but are not well studied in its infection pathway.ConclusionsWe found out a group of proteins which were rich in HCV viral pathway but there were no drugs targeting them according to the drug repurposing hub. It can be concluded that the cluster we obtained from MCODE contains potential targets for HCV treatment and could be implemented for molecular docking and drug designing further by the scientists.
Highlights
Hepatitis C Virus is becoming a major health problem in Asia and across the globe since it is causing serious liver diseases including liver cirrhosis, chronic hepatitis and hepatocarcinoma (HCC)
Based on its associations with host genes, Hepatitis C Virus (HCV) proteins were analyzed in the Cytoscape and it was found out that HCV non-structural protein Non-structural protein 3 (NS3) has the greatest number of interactions with the human genes, i.e., 330 connections
Another group of scientists studied HCV-human interactions experimentally through Yeast 2 Hybrid (Y2H) and did the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway analysis of the human genes interacting with HCV proteins but the difference is that they grouped genes by their interaction with a specific HCV protein and functionally analyzed their percentage involvement in certain biological pathways
Summary
Hepatitis C Virus is becoming a major health problem in Asia and across the globe since it is causing serious liver diseases including liver cirrhosis, chronic hepatitis and hepatocarcinoma (HCC). Hepatitis C Virus or HCV is a small, single-stranded, positive-sense RNA virus belonging to the genus Hepacivirus of Flaviviridae family, discovered in 1989 [1]. It is responsible for severe and chronic liver diseases [2,3,4] and affects 200 million people globally with 17 million cases in Pakistan alone [5, 6]. The non-structural HCV proteins are NS2, NS3, NS4A, NS4B, NS5A and NS5B [2, 9, 10]. Another HCV protein named Frameshift protein or F protein was discovered in the late 90’s [9]
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