Evaluation and annotation of dengue virus variation for genomic surveillance

Abstract

The dengue virus (DENV) is an arthropod-borne virus spread by infected mosquitoes, particularly Aedes aegypti and Aedes albopictus. Prevalent in tropical and subtropical climes, DENV has four different serotypes (DENV-1 to DENV-4) and a genome consisting of a total of 10 distinct proteins. Understanding the variations in the virus’ genome is critical to monitor its development, evaluate vaccination effectiveness and immune escape mechanisms, as well as to predict epidemic potential. Accordingly, this study aimed to investigate variations in these proteins across four DENV serotypes and evaluated their impact on the virus, including whether it acquires or loses functions that enhance its virulence and transmission. Subsequently, these alterations were classified according to their beneficial or detrimental effects on human health by creating a controlled vocabulary. The study focuses on the following five proteins: E, C, M, NS1, and NS2A. Using a biocuration process, DENV protein mutations were annotated using PubMed publications. The results reveal that the E protein was the most extensively investigated regarding mutations, while the M protein received the least studied, which could be attributed to the significant role of the E protein in viral entry and interactions with the host immune response, which establishes it as a primary focus for study. Moreover, the E protein included the most detrimental mutations. By contrast, the NS1 protein showed the greatest number of positive mutations. Finally, DENV type 2 was found to be the most extensively researched serotype among all proteins, which could be due to its role in several significant outbreaks.