Bioinformatics research on the specificity and safety of oncolytic viruses

Abstract

Cancer is a major cause of death worldwide and research on new methods for cancer treatment and prevention is vigorously pursued. Cancer treatment methods using viruses have been found to be effective, and many related studies have been performed. An oncolytic virus is one that can be used effectively in cancer treatment. These viruses selectively infect cancer cells, and cause apoptosis through viral replication and proliferation within the infected cancer cells. They show potential as novel cancer therapeutic agents by selectively killing cancer cells while causing no damage to normal cells. Approximately 40 kinds of oncolytic viruses are now being studied with the aim being their introduction to actual cancer therapeutics. Clinical trials of oncolytic viruses are currently underway, and their anti-cancer effects are being demonstrated. In addition, the types of oncolytic viruses are expected to continuously increase with the continuing development of genetic manipulation techniques. There are different types of oncolytic viruses with diverse and complicated genetic mechanisms of killing cancer cells. In this regard, different researches and analysis methods for each mechanism are required. Correlation analysis between genetic features and anti-cancer mechanisms for each virus also should be performed. Selection and evaluation of viruses for clinical trials will be achieved efficiently if the specificity and safety of oncolytic viruses is studied based on the viral genetic information and their anti-cancer mechanisms. Recent studies focus on revealing new cancer-killing mechanisms of oncolytic viruses, searching for a way to increase anti-cancer effects and evaluating new candidate viruses. To achieve such ends, specific anti-cancer mechanisms of oncolytic viruses should be identified, and research on the viral genome information and genetic mechanisms for interaction between the virus and the antiviral responses of hosts immune system are needed. Data on viral biology and genetics including gene or protein sequences are required to find new candidate viruses and evaluate them. In order to utilize these data, the integration, processing, and storage of scattered data should be performed. Research on the development of cancer therapeutics using viruses is ongoing. However, information about the oncolytic viruses is far from sufficient and no specialized database has yet been accumulated. A database that is specialized for the oncolytic virus should be constructed for processing and analyzing enormous volume of data, then studies on the anti-cancer mechanisms, specificity and safety of oncolytic viruses based on the database can be made. In this study, I present the Oncolytic Virus DataBank (OVDB), which retains important biological information and diverse sequence data that can be obtained at the constructed web interface by establishing gene-based retrieval systems for the viruses and oncolytic viruses. The URL for the constructed database is http://lcbb3.snu.ac.kr/ovdb/. It was created to allow users to utilize various bioinformatics tools for exploring diverse genetic variables that affect cancer-specific killing activity of oncolytic viruses and study genetic mechanisms using the constructed search system. A homology search for gene sequences by inputting a query gene can be performed through the construction of a standalone BLAST server with the database of viral gene sequences. In addition, diverse analysis using sequence information also can be conducted by compilation of web pages to facilitate the use of computational tools for bioinformatics analysis. Multiple sequence alignment (MSA) and phylogenetic analysis based on the constructed database that is specialized for the oncolytic virus were carried out. The result of the generated phylogenetic tree for F genes of adenoviruses was taken as the reference in the present study, then analysis for the result of the generated phylogenetic tree for H genes of measles viruses was performed. Consequently, oncolytic measles virus candidates that target CD46 were suggested. As a result of this study, genetic information for oncolytic viruses can be acquired and bioinformatics analysis can be performed based on the constructed database with a retrieval system for all oncolytic viral species. In addition, the database with a search system can be utilized for the investigation of oncolytic ability of various existing viruses or newly emerged viruses in the future through research using bioinformatics tools. This bioinformatics research based on the constructed database with a data retrieval system and analysis tools open a new research field for the development of novel cancer therapy. This bioinformatics research can be utilized for the development of new anti-cancer therapeutic agents and applied research using oncolytic viruses by providing a foundation of oncolytic virus research and suggesting novel research methods in the field of cancer research.