Recombination of the epsilon determinant and corneal tropism: Human adenovirus species D types 15, 29, 56, and 69.
Viruses within human adenovirus species D (HAdV-D) infect epithelia at essentially every mucosal site. Hypervariable loops 1 and 2 of the hexon capsid protein contain epitopes that together form the epsilon determinant for serum neutralization. We report our analyses comparing HAdV-D15, 29, 56, and the recently identified type 69, each with highly similar hexons and the same serum neutralization profile, but otherwise disparate genomes. Of these, only HAdV-D type 56 is associated with epidemic keratoconjunctivitis (EKC), a severe infection of ocular surface epithelium and underlying corneal stroma. In the mouse adenovirus keratitis model, all four viruses induced inflammation. However, HAdV-D56 entry into human corneal epithelial cells and fibroblasts in vitro dramatically exceeded that of the other three viruses. We conclude that the hexon epsilon determinant is not a prime contributor to corneal tropism.
Department of Ophthalmology, Howe Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, United States.
Gurdeep
G
Singh
Department of Ophthalmology, Howe Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, United States.
Xiaohong
X
Zhou
Department of Ophthalmology, Howe Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, United States.
Jeong Yoon
JY
Lee
Department of Ophthalmology, Howe Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, United States.
Mohammad A
MA
Yousuf
Department of Ophthalmology, Howe Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, United States.
Mirja
M
Ramke
Department of Ophthalmology, Howe Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, United States.
Ashrafali M
AM
Ismail
Department of Ophthalmology, Howe Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, United States.
Ji Sun
JS
Lee
Department of Ophthalmology, Howe Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, United States.
Christopher M
CM
Robinson
Bioinformatics and Computational Biology Program, School of Systems Biology, George Mason University, Manassas, VA, United States.
Donald
D
Seto
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
David W
DW
Dyer
Division of Infectious Diseases, Naval Medical Center San Diego, San Diego, CA, United States.
Morris S
MS
Jones
Department of Ophthalmology, Howe Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, United States. Electronic address: jaya_rajaiya@meei.harvard.edu.
Jaya
J
Rajaiya
Department of Ophthalmology, Howe Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, United States. Electronic address: james_chodosh@meei.harvard.edu.
James
J
Chodosh
D000260:Adenoviruses, Human / Q000145:classification* / Q000502:physiology*; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics* / Q000276:immunology*; D002460:Cell Line; D003315:Cornea / Q000821:virology; D004195:Disease Models, Animal; D000939:Epitopes / Q000235:genetics* / Q000276:immunology*; D016679:Genome, Viral; D006801:Humans; D007634:Keratitis / Q000473:pathology / Q000821:virology; D007637:Keratoconjunctivitis / Q000473:pathology / Q000821:virology; D051379:Mice; D010802:Phylogeny; D011995:Recombination, Genetic; D056189:Viral Tropism
D036022:Capsid Proteins; D000939:Epitopes; C018315:hexon capsid protein, Adenovirus
Adenovirus; Epidemic keratoconjunctivitis; Homologous recombination; Keratitis