Evidence of molecular evolution driven by recombination events influencing tropism in a novel human adenovirus that causes epidemic keratoconjunctivitis

In 2005, a human adenovirus strain (formerly known as HAdV-D22/H8 but renamed here HAdV-D53) was isolated from an outbreak of epidemic keratoconjunctititis (EKC), a disease that is usually caused by HAdV-D8, -D19, or -D37, not HAdV-D22. To date, a complete change of tropism compared to the prototype...

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Bibliographic Details
Published in:	PloS one 2009-06, Vol.4 (6), p.e5635-e5635
Main Authors:	Walsh, Michael P, Chintakuntlawar, Ashish, Robinson, Christopher M, Madisch, Ijad, Harrach, Balázs, Hudson, Nolan R, Schnurr, David, Heim, Albert, Chodosh, James, Seto, Donald, Jones, Morris S
Format:	Article
Language:	eng
Subjects:	Adenovirus Adenoviruses Adenoviruses, Human - genetics Adenoviruses, Human - metabolism Analysis Animals Base Sequence Binding sites Bioinformatics Biological evolution Computational Biology - methods Cornea Cytokines Deoxyribonucleic acid Disease DNA Epidemics Evolution Evolution, Molecular Evolutionary Biology Genes Genetics Genetics and Genomics/Bioinformatics Genome, Viral Genomes Genomics Herpes viruses Human adenovirus Humans Keratoconjunctivitis Keratoconjunctivitis - etiology Keratoconjunctivitis - virology Laboratories Mice Mice, Inbred C57BL Microbiology/Microbial Evolution and Genomics Models, Genetic Molecular biology Molecular Biology/Bioinformatics Molecular Biology/Recombination Molecular evolution Molecular Sequence Data Neutralization Ophthalmology Outbreaks Pandemics Phylogenetics Phylogeny Proteins Recombination Recombination, Genetic Respiratory diseases Sequence Homology, Nucleic Acid Trends Tropism Viral proteins Virology Virology/Emerging Viral Diseases Virulence (Microbiology) Viruses
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Summary:	In 2005, a human adenovirus strain (formerly known as HAdV-D22/H8 but renamed here HAdV-D53) was isolated from an outbreak of epidemic keratoconjunctititis (EKC), a disease that is usually caused by HAdV-D8, -D19, or -D37, not HAdV-D22. To date, a complete change of tropism compared to the prototype has never been observed, although apparent recombinant strains of other viruses from species Human adenovirus D (HAdV-D) have been described. The complete genome of HAdV-D53 was sequenced to elucidate recombination events that lead to the emergence of a viable and highly virulent virus with a modified tropism. Bioinformatic and phylogenetic analyses of this genome demonstrate that this adenovirus is a recombinant of HAdV-D8 (including the fiber gene encoding the primary cellular receptor binding site), HAdV-D22, (the epsilon determinant of the hexon gene), HAdV-D37 (including the penton base gene encoding the secondary cellular receptor binding site), and at least one unknown or unsequenced HAdV-D strain. Bootscanning analysis of the complete genomic sequence of this novel adenovirus, which we have re-named HAdV-D53, indicated at least five recombination events between the aforementioned adenoviruses. Intrahexon recombination sites perfectly framed the epsilon neutralization determinant that was almost identical to the HAdV-D22 prototype. Additional bootscan analysis of all HAdV-D hexon genes revealed recombinations in identical locations in several other adenoviruses. In addition, HAdV-D53 but not HAdV-D22 induced corneal inflammation in a mouse model. Serological analysis confirmed previous results and demonstrated that HAdV-D53 has a neutralization profile representative of the epsilon determinant of its hexon (HAdV-D22) and the fiber (HAdV-D8) proteins. Our recombinant hexon sequence is almost identical to the hexon sequences of the HAdV-D strain causing EKC outbreaks in Japan, suggesting that HAdV-D53 is pandemic as an emerging EKC agent. This documents the first genomic, bioinformatic, and biological descriptions of the molecular evolution events engendering an emerging pathogenic adenovirus.
ISSN:	1932-6203 1932-6203