Virulence network of interacting domains of influenza a and mouse proteins

Abstract

There exist several databases that provide virus-host protein interactions. While most provide curated records of interacting virus-host protein pairs, information on the strain-specific virulence factors or protein domains involved, is lacking. Some databases offer incomplete coverage of influenza strains because of the need to sift through vast amounts of literature (including those of major viruses including HIV and Dengue, besides others). None have offered complete, strain specific protein-protein interaction records for the influenza A group of viruses. In this paper, we present a comprehensive network of predicted domain-domain interaction(s) (DDI) between influenza A virus (IAV) and mouse host proteins, that will allow the systematic study of disease factors by taking the virulence information (lethal dose) into account. From a previously published dataset of lethal dose studies of IAV infection in mice, we constructed an interacting domain network of mouse and viral protein domains as nodes with weighted edges. The edges were scored with the Domain Interaction Statistical Potential (DISPOT) to indicate putative DDI. The virulence network can be easily navigated via a web browser, with the associated virulence information (LD₅₀ values) prominently displayed. The network will aid influenza A disease modeling by providing strain-specific virulence levels with interacting protein domains. It can possibly contribute to computational methods for uncovering influenza infection mechanisms mediated through protein domain interactions between viral and host proteins. It is available at https://iav-ppi.onrender.com/home.

Keywords: domain-domain interaction; influenza a; lethal dose 50; mouse model; protein; virulence.