Role of adenovirus type 5 early region 3 in the pathogenesis of ocular disease and cell culture infection.
Experimental animal virus replication models make it possible to study the role of viral gene products in adenovirus (Ad)-induced ocular disease. This study tested the hypothesis that the early region 3 (E3) of the human Ad genome plays an important role in the pathogenesis of Ad-induced ocular disease. Both Ad5 wt300, a genetically defined E3+ parent, and Ad5 dl327, a deletion mutant without E3 (E3-), replicated in ocular-derived cell cultures. Ad5 E3+ and Ad8 replicated more efficiently than did Ad5 E3- in cornea and conjunctival cell cultures. Lacrimal gland-derived cell cultures supported human Ad8 replication significantly more efficiently than did either Ad5 E3+ or Ad5 E3-. After intrastromal and topical inoculation of rabbits with either Ad wt300 or Ad dl327, a specific immune response was elicited that coincided with the appearance of subepithelial opacities that mimicked human disease both clinically and histologically. The clinical features (i.e., conjunctivitis, iritis, and corneal edema) were not significantly different for Ad5 E3(+)- and Ad5 E3(-)-induced ocular infection. Ad5 E3(+)- and Ad5 E3(-)-inoculated eyes shed virus for up to 7 and 5 days, respectively, and occasionally established persistent and/or latent infections in corneal, conjunctival, and, infrequently, lacrimal gland cells. Both Ad5 E3+ and Ad5 E3- spread from virus-inoculated animals to the cornea and conjunctiva of normal animals. Under current experimental conditions, expression of the E3 gene does not appear to affect the degree of virulence in ocular disease induced by Ad5 in the rabbit eye model. Deletion of the E3 gene from Ad5 does not make the model more like human disease.
Trousdale
M D
MD
Doheny Eye Institute, Los Angeles, CA 90033, USA.
Nóbrega
R
R
Stevenson
D
D
Nakamura
T
T
dos Santos
P M
PM
Labree
L
L
McDonnell
P J
PJ
D000208:Acute Disease; D017503:Adenovirus E3 Proteins / Q000235:genetics / Q000502:physiology*; D000258:Adenovirus Infections, Human / Q000209:etiology* / Q000473:pathology; D000260:Adenoviruses, Human / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D002872:Chromosome Deletion; D002908:Chronic Disease; D003228:Conjunctiva / Q000473:pathology / Q000821:virology; D003315:Cornea / Q000473:pathology / Q000821:virology; D004848:Epithelium / Q000821:virology; D015828:Eye Infections, Viral / Q000209:etiology* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D005814:Genes, Viral; D007639:Keratoconjunctivitis, Infectious / Q000473:pathology / Q000821:virology*; D007765:Lacrimal Apparatus / Q000473:pathology / Q000821:virology; D011817:Rabbits; D014774:Virulence; D014779:Virus Replication / Q000502:physiology
D017503:Adenovirus E3 Proteins