Systematic annotation and analysis of “virmugens”—Virulence factors whose mutants can be used as live attenuated vaccines

Abstract

Live attenuated vaccines are usually generated by mutation of genes encoding virulence factors. “Virmugen” is coined here to represent a gene that encodes for a virulent factor of a pathogen and has been proven feasible in animal models to make a live attenuated vaccine by knocking out this gene. Not all virulence factors are virmugens. VirmugenDB is a web-based virmugen database (http://www.violinet.org/virmugendb). Currently, VirmugenDB includes 225 virmugens that have been verified to be valuable for vaccine development against 57 bacterial, viral, and protozoan pathogens. Bioinformatics analysis has revealed significant patterns in virmugens. For example, 10 Gram-negative and one Gram-positive bacterial aroA genes are virmugens. A sequence analysis has revealed at least 50% of identities in the protein sequences of the 10 Gram-negative bacterial aroA virmugens. As a pathogen case study, Brucella virmugens were analyzed. Out of 15 verified Brucella virmugens, six are related to carbohydrate or nucleotide transport and metabolism, and two involving cell membrane biogenesis. In addition, 54 virmugens from 24 viruses and 12 virmugens from 4 parasites are also stored in VirmugenDB. Virmugens tend to involve metabolism of nutrients (e.g., amino acids, carbohydrates, and nucleotides) and cell membrane formation. Host genes whose expressions were regulated by virmugen mutation vaccines or wild type virulent pathogens have also been annotated and systematically compared. The bioinformatics annotation and analysis of virmugens helps elucidate enriched virmugen profiles and the mechanisms of protective immunity, and further supports rational vaccine design.

Characterization of the Molecular Interplay between Moraxella catarrhalis and Human Respiratory Tract Epithelial Cells

“…The aroA gene encodes a 3-phosphoshikimate 1-carboxyvinyltransferase that is involved in aromatic amino acid metabolism and generation of chorismate-derived metabolites [31]. Deletion of aro genes leads to attenuated virulence in many bacterial pathogens and often results in defective cell envelope biosynthesis [32]. It could be possible that a defective outer membrane function in M.…”

DNAVaxDB: the first web-based DNA vaccine database and its data analysis

“…We have previously identified another group of microbial genes called "virmugens", which is coined to represent a gene that encodes for a pathogen virulence factor and has been proven feasible in at least one animal model to make a live attenuated vaccine after this gene is knocked out [25]. It has been known that virulence or pathogenic factors can often be used as protective antigens [26].…”

Ontology-Based Vaccine and Drug Adverse Event Representation and Theory-Guided Systematic Causal Network Analysis Toward Integrative Pharmacovigilance Research

“…Figure 3 illustrates how VO logically represents the information of an influenza vaccine (Afluria), including how the vaccine links to the vaccinee, vaccination route, vaccine quality, vaccine allergen, the manufacturer, influenza virus pathogen, and vaccine-induced immune responses. VO has been used in different applications to represent various types of vaccine-related information [22, 25–27, 59]. The VO has also been used for many studies in vaccine literature mining [23, 29, 60–62].…”