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Journal of Virology, February 2005, p. 2559-2572, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2559-2572.2005

Genomic and Bioinformatics Analysis of HAdV-4, a Human Adenovirus Causing Acute Respiratory Disease: Implications for Gene Therapy and Vaccine Vector Development

Anjan Purkayastha,^1,2,3 Susan E. Ditty,^2,4, Jing Su,^1,2,3 John McGraw,^2,4 Ted L. Hadfield,^2,4, Clark Tibbetts,^2,3 and Donald Seto^1,2,3*

Bioinformatics and Computational Biology, School of Computational Sciences, George Mason University, Manassas,¹ HQ USAF Surgeon General Office, Directorate of Modernization,³ Epidemic Outbreak Surveillance Consortium, Falls Church, Virginia,² Division of Microbiology, Department of Infectious and Parasitic Diseases Pathology, Armed Forces Institute of Pathology, Washington, D.C.⁴

Received 16 June 2004/ Accepted 13 October 2004

Human adenovirus serotype 4 (HAdV-4) is a reemerging viral pathogenic agent implicated in epidemic outbreaks of acute respiratory disease (ARD). This report presents a genomic and bioinformatics analysis of the prototype 35,990-nucleotide genome (GenBank accession no. AY594253). Intriguingly, the genome analysis suggests a closer phylogenetic relationship with the chimpanzee adenoviruses (simian adenoviruses) rather than with other human adenoviruses, suggesting a recent origin of HAdV-4, and therefore species E, through a zoonotic event from chimpanzees to humans. Bioinformatics analysis also suggests a pre-zoonotic recombination event, as well, between species B-like and species C-like simian adenoviruses. These observations may have implications for the current interest in using chimpanzee adenoviruses in the development of vectors for human gene therapy and for DNA-based vaccines. Also, the reemergence, surveillance, and treatment of HAdV-4 as an ARD pathogen is an opportunity to demonstrate the use of genome determination as a tool for viral infectious disease characterization and epidemic outbreak surveillance: for example, rapid and accurate low-pass sequencing and analysis of the genome. In particular, this approach allows the rapid identification and development of unique probes for the differentiation of family, species, serotype, and strain (e.g., pathogen genome signatures) for monitoring epidemic outbreaks of ARD.

Present address: Midwest Research Institute, Palm Bay, FL 32909.

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