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. 2023 Feb 17:3:1123993.
doi: 10.3389/fbinf.2023.1123993. eCollection 2023.

Virulence network of interacting domains of influenza a and mouse proteins

Teng Ann Ng  1 , Shamima Rashid  1 , Chee Keong Kwoh  1
Affiliations

Virulence network of interacting domains of influenza a and mouse proteins

Teng Ann Ng et al. Front Bioinform. .

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.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
IAV particle and its fully assembled constituent proteins. Genomic RNA segments are shown in green, wrapped around nucleoproteins. The hetero-trimeric RNA-dependent RNA polymerase complex comprising of PB1, PB2, and PA is shown in orange, light and dark blue circles. This figure is by Jung and Lee (Jung and Lee, 2020).
FIGURE 2
FIGURE 2
Implementation procedure.
FIGURE 3
FIGURE 3
Cross-tabulation of IAV subtypes and mouse strains, colored according to three-class virulence classification problem. ‘Others’ refers to the aggregation of infection records from IAV subtypes—H1N2, H3N8, H5N2, H5N5, H5N6, H5N8, H7N2, H7N3, H7N7, and H7N9.
FIGURE 4
FIGURE 4
Proportion of all wild-type/laboratory IAV strains, separated into with and without taxonomy ID numbers, against remaining records (green bars) in the cleaned dataset. Infection records involving wild-type IAV where taxonomy ID number could not be found (orange bars) were omitted, reducing the number of infection records to 166 (blue bars). “Cleaned” refers to the final dataset of 139 infection records (green bars) available in IAV-Mouse PPI database, where each record corresponds to a unique combination of IAV and mouse strain.
FIGURE 5
FIGURE 5
(A) GUI functionality navigation. (B) Screenshot of GUI layout.
See this image and copyright information in PMC

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