Construction and analysis of a comprehensive protein interaction network of HCV with its host Homo sapiens

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). Protein interaction networks presents us innumerable novel insights into functional constitution of proteome and helps us finding potential candidates for targeting the drugs.

Here 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.

We 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.

We 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.