@article {1364579,
	title = {Analysis of human adenovirus type 19 associated with epidemic keratoconjunctivitis and its reclassification as adenovirus type 64},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {53},
	number = {6},
	year = {2012},
	month = {2012 May 14},
	pages = {2804-11},
	abstract = {PURPOSE: Human adenovirus species D type 19 (HAdV-D19) has been associated with epidemic keratoconjunctivitis (EKC), a highly inflammatory infection of the ocular surface. Confusion exists regarding the origins of HAdV-D19. The prototype virus (HAdV-D19p) does not cause EKC, while a virus identified later with the identical serologic determinant is a significant ocular pathogen. METHODS: High throughput genome sequencing and bioinformatics analysis were performed on HAdV-D19p and three HAdV-D19 EKC strains, and compared to the previously sequenced clinical isolate, HAdV-D19 (C) and HAdV-D37. Corneas of C57BL/6J mice were injected with HAdV-D19p, HAdV-D19 (C), or virus-free buffer, and inflammation assessed by clinical examination, flow cytometry, and cytokine ELISA. Confocal microscopy and real-time PCR of infected corneal cell cultures were used to test viral entry. RESULTS: HAdV-D19 (C) and the other clinical EKC isolates showed nearly 100\% sequence identity. EKC strains diverged from HAdV-D19p in the penton base, E3, and fiber transcription units. Simplot analysis showed recombination between EKC-associated HAdV-D19 with HAdV-D37, HAdV-D22, and HAdV-D19p, the latter contributing only the hexon gene, the principal serum neutralization determinant. HAdV-D19p induced stromal keratitis in the C57BL/6J mouse, but failed to infect productively human corneal epithelial cells. These data led to retyping of the clinical EKC isolates with a HAdV-D19 hexon gene as HAdV-D64. CONCLUSIONS: HAdV-D19 associated with EKC (HAdV-D64) originated from a recombination between HAdV-D19p, HAdV-D37, and HAdV-D22, and was mischaracterized because of a shared hexon gene. HAdV-D19p is not infectious for corneal epithelial cells, thus explaining the lack of any association with keratitis.},
	keywords = {Adenovirus Infections, Human, Adenoviruses, Human, Animals, DNA, Viral, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Genome, Viral, Humans, Keratoconjunctivitis, Mice, Mice, Inbred C57BL, Sequence Analysis, DNA},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-9656},
	author = {Zhou, Xiaohong and Robinson, Christopher M and Rajaiya, Jaya and Dehghan, Shoaleh and Seto, Donald and Jones, Morris S and Dyer, David W and Chodosh, James}
}
