HCVIVdb: The hepatitis-C IRES variation database.

Evan W Floden,Martin Pospíšek,Václav Vopálenský,Anas Khawaja

doi:10.1186/s12866-016-0804-6

Abstract

BackgroundSequence variability in the hepatitis C virus (HCV) genome has led to the development and classification of six genotypes and a number of subtypes. The HCV 5′ untranslated region mainly comprises an internal ribosomal entry site (IRES) responsible for cap-independent synthesis of the viral polyprotein and is conserved among all HCV genotypes.DescriptionConsidering the possible high impact of variations in HCV IRES on viral protein production and thus virus replication, we decided to collect the available data on known nucleotide variants in the HCV IRES and their impact on IRES function in translation initiation. The HCV IRES variation database (HCVIVdb) is a collection of naturally occurring and engineered mutation entries for the HCV IRES. Each entry contains contextual information pertaining to the entry such as the HCV genotypic background and links to the original publication. Where available, quantitative data on the IRES efficiency in translation have been collated along with details on the reporter system used to generate the data. Data are displayed both in a tabular and graphical formats and allow direct comparison of results from different experiments. Together the data provide a central resource for researchers in the IRES and hepatitis C-oriented fields.ConclusionThe collation of over 1900 mutations enables systematic analysis of the HCV IRES. The database is mainly dedicated to detailed comparative and functional analysis of all the HCV IRES domains, which can further lead to the development of site-specific drug designs and provide a guide for future experiments. HCVIVdb is available at http://www.hcvivdb.org.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0804-6) contains supplementary material, which is available to authorized users.

Highlights

Sequence variability in the hepatitis C virus (HCV) genome has led to the development and classification of six genotypes and a number of subtypes
The database is mainly dedicated to detailed comparative and functional analysis of all the HCV internal ribosomal entry site (IRES) domains, which can further lead to the development of site-specific drug designs and provide a guide for future experiments
The natural and engineered variations in the domains (I-IV) of the HCV IRES can impact the efficiency of its translation; the compilation of both kinds of mutations provided by the database can facilitate targeted drug design

Summary

Conclusion

HCVIVdb is a specialized relational database that focuses on the reported variations of the HCV IRES that have been found in patients and/or purposely introduced to the viral genome and on the impact of these variations on HCV IRES activity. The HCVIVdb is an efficient and helpful tool for people working in both the HCV and IRES fields and can aid in the understanding of the IRES function, development and design of new experiments and in a targeted drug design. Scientists are encouraged to submit their data concerning HCV IRES mutations either through the dedicated form within the HCVIVdb web site or directly to the corresponding author. Abbreviations HCV, hepatitis C virus; IRES, internal ribosomal entry site; MSA, multiple sequence alignment. All authors critically analyzed the results, read and approved the final version of the manuscript. Author details 1Department of Genetics & Microbiology, Faculty of Science, Charles University in Prague, Viničná 5, 128 44 Prague 2, Czech Republic.

Findings

Background