Computational Analysis of Human Adenovirus Evolution and Development of Bioinformatics Tools

Abstract

Human adenoviruses (HAdVs) may be highly contagious and may be human pathogens that can cause a wide range of illnesses including respiratory, gastrointestinal and ocular infections. Individuals with immune deficiency are especially prone to such infections, leading to fatalities. Even though adenoviruses continue to cause concerns due to notable mortality and morbidity in human populations, their existence may also provide a possible benefit for patients with a broader range of illnesses as well. In recent studies, for example, adenoviruses have been used in gene therapy and vaccine vector development. Recently, bioinformatics and genomics are both high-resolution approaches and resources available for studying the adenovirus for such purposes. One observation is that genome recombination is a driving force in the molecular evolution of human adenoviruses. This has implications for their use as vectors, particular across host species. Computational analysis of this event can provide a better understanding of the role recombination plays in the human adenovirus evolution and pathology, which may later provide for a rational design of vaccines and for gene delivery vector development. Custom developed bioinformatics tools will also help to facilitate the process of data mining and analysis, and its presentation. In the course of this project, the genomes of three respiratory and gastrointestinal pathogens, HAdV-B16, B21, D58 and D59, were analyzed using bioinformatics tools to understand their origins and evolution as pathogens, in particular, changes in their genomes. To facilitate this, several tools were developed to assist this genome analysis. The analysis of both HAdV-B16 and HAdV-B21, archived 1950s prototypes, provided examples of “then novel and emergent” HAdVs arising as the result of genome recombination events with simian adenoviruses, across host species. Recently emergent HAdV-D58 and HAdV-D59 are novel pathogens that are characterized by genome sequencing and analysis. Their results have shown also that recombination plays an important role in their molecular evolution.