March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Mistyping of Human Adenovirus Type 19 Associated with Epidemic Keratoconjunctivitis
Author Affiliations & Notes
  • Xiaohong Zhou
    Ophthalmology, Mass Eye and Ear - Harvard Medical School, Boston, Massachusetts
  • Christopher M. Robinson
    Ophthalmology, Mass Eye and Ear - Harvard Medical School, Boston, Massachusetts
  • Jaya Rajaiya
    Ophthalmology, Mass Eye and Ear - Harvard Medical School, Boston, Massachusetts
  • Donald Seto
    School of Systems Biology, George Mason University, Manassas, Virginia
  • Morris S. Jones
    Viral and Rickettsial Disease Laboratory, California Department of Public Health, Richmond, California
  • David W. Dyer
    Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma
  • James Chodosh
    Ophthalmology, Mass Eye and Ear - Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Xiaohong Zhou, None; Christopher M. Robinson, None; Jaya Rajaiya, None; Donald Seto, None; Morris S. Jones, None; David W. Dyer, None; James Chodosh, Alcon, Allergan (R), Alcon, Allergan, Bausch & Lomb (C)
  • Footnotes
    Support  NIH grants EY013124 and P30EY014104, and an unrestricted grant to the Department of Ophthalmology, Harvard Medical School from Research to Prevent Blindness, Inc., NY, NY.
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6157. doi:
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      Xiaohong Zhou, Christopher M. Robinson, Jaya Rajaiya, Donald Seto, Morris S. Jones, David W. Dyer, James Chodosh; Mistyping of Human Adenovirus Type 19 Associated with Epidemic Keratoconjunctivitis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6157.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Human adenovirus species D type 19 (HAdV-D19) is associated with epidemic keratoconjunctivitis (EKC), an acute and highly inflammatory infection of the cornea and conjunctiva with considerable morbidity. However, confusion exists regarding the origins and corneal tropism of HAdV-D19. The prototype virus (HAdV-D19p) has not been isolated from patients with EKC, while a virus identified later with the identical serologic determinant is a significant EKC pathogen.

Methods: : High throughput sequencing, global pairwise genome alignment, and bioinformatics analysis was performed on HAdV-D19p and three strains of HAdV-D19 isolated directly from patients with EKC, and compared to a previously characterized clinical isolate (HAdV-D19 (C)) and the closely related HAdV-D37. Corneas of C57BL/6J mice were injected intrastromally with HAdV-D19p, HAdV-D19 (C), or virus-free dialysis buffer, and assessed by clinical examination, flow cytometry, and ELISA. Confocal microscopy and real-time PCR of infected corneal cell cultures were used to assess viral entry and DNA replication, respectively.

Results: : Whole genome-wide comparisons revealed near 100% sequence identity between HAdV-D19 (C) and the three EKC clinical isolates newly sequenced. In contrast, HAdV-D19p nucleotide sequence diverged from clinical EKC isolates in the penton base, E3, and fiber protein coding regions. Simplot analysis showed that EKC-associated HAdV-D19 is actually a naturally occurring recombinant of HAdV-D37, HAdV-D22, and HAdV-D19p, the latter contributing only the hexon gene, which contains the serotype determinant. Surprisingly, HAdV-D19p induced significant inflammation in the C57BL/6J mouse adenovirus stromal keratitis model, but infection of corneal cell lines showed that HAdV-D19p does not infect human corneal epithelial cells.

Conclusions: : HAdV-D19 strains associated with EKC originated from a recombination between HAdV-D19p, HAdV-D37, and HAdV-D22. Although highly inflammatory in the corneal stroma, HAdV-D19p is not infectious for corneal epithelial cells, thus explaining its lack of an association with keratitis. Based on recently revised GenBank criteria, EKC-associated HAdV-D19 should be retyped.

Keywords: adenovirus • keratitis • genetics 

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