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2009
OMIG, Abstract 24
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Human Adenovirus Type D53: Molecular Evolution Influencing Tropism.
J. Chodosh1, M.P. Walsh2, A.V. Chintakuntlawar1, C.M. Robinson1, I. Madisch3, B. Harrach4, N.R. Hudson5, D. Schnurr6, A. Heim3, D Seto2, M.S. Jones5
1Mass Eye and Ear Infirmary – Harvard Medical School, 2George Mason University, 3Insitut für Virologie – Medizinische Hochschule, 4Veterinary Med. Res. Inst. - Hungarian Academy of Sciences, 5David Grant USAF Medical Center – Travis AFB, 6Viral and Rickettsial Disease Laboratory – California Dept. of Public Health
Purpose: In 2005, a human adenovirus strain identified by serotyping as an HAdV-D22/H8 intermediate, was isolated from an outbreak of epidemic keratoconjunctivitis (EKC), a disease that is usually caused by HAdV-D8, D19, or D37, not HAdV-D22.
Methods: The complete genome of this new clinical isolate was sequenced and analyzed and the virus used in a novel mouse model of adenovirus keratitis.
Results: Bioinformatic and phylogenetic analyses of the viral genome demonstrated recombination of HAdV-D8 (the fiber gene encoding the primary cellular receptor binding site), HAdV-D22, (the epsilon determinant of the hexon gene), HAdV-D37 (the penton base gene encoding the secondary cellular receptor binding site), and at least one previously unsequenced HAdV-D strain. Bootscan analysis of the complete genomic sequence of this novel adenovirus, which we 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. The recombinant hexon sequence was found to be 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.
Conclusions: This documents the first genomic, bioinformatic, and biological descriptions of the molecular evolution events engendering an emerging pathogenic adenovirus.
Disclosure code: N
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