A Review and Meta-Analysis of Influenza Interactome Studies

Abstract

Annually, the influenza virus causes 500,000 deaths worldwide. Influenza-associated mortality and morbidity is especially high among the elderly, children, and patients with chronic diseases. While there are antivirals available against influenza, such as neuraminidase inhibitors and adamantanes, there is growing resistance against these drugs. Thus, there is a need for novel antivirals for resistant influenza strains. Host-directed therapies are a potential strategy for influenza as host processes are conserved and are less prone mutations as compared to virus-directed therapies. A literature search was performed for papers that performed viral-host interaction screens and the Reactome pathway database was used for the bioinformatics analysis. A total of 15 studies were curated and 1717 common interactors were uncovered among all these studies. KEGG analysis, Enrichr analysis, STRING interaction analysis was performed on these interactors. Therefore, we have identified novel host pathways that can be targeted for host-directed therapy against influenza in our review.

Keywords: bioinformatics; host-pathogen interactions; influenza; influenza proteins; interactome analysis.

Figure 1

Bioinformatics analysis of influenza and host interactors. HPIDB: Human Pathogen Interactions Database. Host interactors of influenza were separated into known and newly determined interactions. PubMed search of Viral–host interactome studies (IP-MS, Y2H, computer homology) was conducted. Papers were filtered if they were in English and full data set was available for analysis. Compiled data set of interactors was analyzed using STRING, Gene set enrichment analysis, and KEGG pathway.

Figure 2

Summary of the main processes found to be represented for each viral protein. (A) Enriched KEGG pathway for interactors of each viral protein (B) GO analysis of interactors of each viral protein. Proteins were analyzed using Enrichr BP, MF, and CC represent Biological Process, Molecular Function, and Cellular Component groups of gene ontology (GO).

Figure 3

A network analysis of influenza proteins and host proteins involved in ER protein processing. Proteins classified as belonging to the ER protein processing pathway were analyzed by STRING database. The viral proteins are represented by orange triangles and host interactors are represented by green hexagons. Each interaction is represented by edges connecting the two nodes with the arrow reflecting a positive association between two proteins.