Vitronectin: a possible determinant of adenovirus type 19 tropism for human corneal epithelium.
OBJECTIVE
Adenoviruses typically demonstrate specific tissue tropisms, as in the association of Ad19 with epidemic keratoconjunctivitis. We sought to determine factors that might influence the apparent tropism of Ad19 for the cornea.


METHODS
Laboratory investigation.


METHODS
Adenovirus serotypes Ad2, 5, 9, 10, 11, 13, and 19 were compared for their capacity to replicate in human corneal epithelial cells (HCECs) in culture. Organotypically cultured human corneas were infected with Ad19 or Ad2, and viral titers were compared after 7 days. Replication of both viruses was compared in HCECs cultured on various extracellular matrices. Western blot analysis and immunohistochemistry were applied to human donor corneas and HCECs.


RESULTS
One week after infection of HCEC monolayer cultures, Ad2 titers were significantly higher than any of the other viruses tested (P <.05). In organotypic corneal cultures, Ad19 titers were significantly higher than Ad2 (P = .0003). Ad2 replication in HCECs equaled or exceeded that of Ad19 on all extracellular matrices except vitronectin, where Ad2 replication was reduced and Ad19 replication enhanced (P <.0001). Vitronectin was detected by immunohistochemistry within the corneal epithelial basement membranes of human donor corneas. Increased alpha(v) integrin expression and greater tyrosine kinase phosphorylation in HCECs cultured on vitronectin were demonstrated by Western blot analysis.


CONCLUSIONS
In vitro, vitronectin enhances growth of Ad19, possibly by up-regulation of receptor alpha(v) integrins and increased activity of tyrosine kinases necessary for adenoviral internalization. We hypothesize that differential tissue tropisms for adenoviruses may derive in part from tissue-specific extracellular matrix expression.
Xiao
Jingnan
J
Molecular Pathogenesis of Eye Infection Research Center, Dean A. McGee Eye Institute, Department of Ophthalmology, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Boulevard, Oklahoma City, OK 73104, USA.
Natarajan
Kanchana
K
Nataraja
Kanchana
K
Rajala
Maitreyi S
MS
Astley
Roger A
RA
Ramadan
Raniyah T
RT
Chodosh
James
J
D000260:Adenoviruses, Human / Q000502:physiology*; D015153:Blotting, Western; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D019573:Epithelium, Corneal / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D039564:Integrin alphaV / Q000378:metabolism; D010766:Phosphorylation; D018523:Tropism / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology; D019096:Vitronectin / Q000502:physiology*
D039564:Integrin alphaV; D019096:Vitronectin; D014443:Tyrosine