Sequencing of Human Adenovirus Clinical Isolates From Recent and Reference Genomes

Human adenoviruses (HAdV) are pathogens causing a range of human infectious diseases, including respiratory, ocular, gastrointestinal, renal and metabolic. HAdV infections can be highly contagious, causing high morbidity rate and mortality rates and result in outbreaks. They are also a model organism in the research laboratory for cell and molecular biology.

The goal of this project is to understand HAdV biology, especially the evolution and emergence of new and highly pathogenic serotypes and to provide targets for therapeutic development. Recent genome studies of several HAdVs have provided insight into the molecular mechanisms of evolution and emerging HAdV pathogens. This project extends these single genome studies, and serves as a model in understanding a pathogen with a wide range of pathologies in extraordinary detail based on genomics and bioinformatics, complementing the resources already provided by a multitude of researchers. There are 31 prototype and 37 clinical isolates genomes currently deposited in GenBank, with 55 defined total prototypes partitioned into seven species. For this project we will sequence and analyze approximately 100 HAdV genomes that represent 24 prototypes as well as recently isolated and archived clinical strains that were characterized using classical methods. These strains will provide further insight into the tissue trophism of this human pathogen,explaining HAdV evolution, pathogenicity, virulence and host/tissue adaptation.

The analysis of these HAdV genomes will specifically provide the following genomic resources: 1) appropriate diagnostic probes for molecular typing assays; 2) pathogen genome signatures for microarray development; 3) understanding of epitope stability for vaccine development and application; 4) SNP data for natural variation studies; and 5) database of genomes relevant to the continuing use and development of HAdV as gene therapy and gene delivery vectors.

The public health and medical sectors, both civilian and military, are actively working on HAdV pathogens, defining outbreaks and trying to identify the pathogens. An extensive set of reference and clinical isolate genomes, as proposed here, will expedite their work by providing "state-or-the-art" data and resources to complement and extend their observations. The development of rational and appropriate vaccines is a priority for limiting the effects of HAdV globally.

White Paper Access

The initial white paper submitted can be downloaded here. Since white papers are not always approved exactly as submitted, this document may not exactly describe the final form of the project. Please contact gsc@jcvi.org if you have any questions.

Funding