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K. A. Yates, S. A. K. Harvey, E. G. Romanowski, Y. J. Gordon; Comparative Effects of Adenovirus Serotypes 19 and 5 on Human Corneal Epithelial Cells: Microarray Analysis of Host Cell Response. Invest. Ophthalmol. Vis. Sci. 2008;49(13):491.
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© ARVO (1962-2015); The Authors (2016-present)
Adenovirus (Ad) is the major cause of viral conjunctivitis worldwide. We previously examined the transcriptomic responses of human conjunctival cells to ocular isolates of the respiratory Ad serotype 5 (Ad5: IOVS 46, 3657-3665, 2005) and the oculotropic serotype Ad19 (IOVS 47, ARVO E-abstract 3047, 2006). We now extend this experimental format to human corneal epithelial cells (HCEC).
HCEC in primary culture were infected with Ad5 or Ad19 at multiplicities of infection (MOI) of 0, 0.1 or 1.0 and harvested at 1.5h or 16h post- infection. Total cell RNA was isolated, processed and analyzed using Affymetrix HU133 Plus 2.0 chips with 54,675 panels (specific transcript sequences). For each time point we compared infected samples with the uninfected control, selecting panels with a 2-fold or better response.
At 16h, the numbers of panels altered were: Ad19 MOI 1.0, 3377; Ad5 MOI 1.0, 2363; Ad19 MOI 0.1, 1928; and Ad5 MOI 0.1, 1405. We focused on panels showing responses in all four conditions (i.e., common effects: 479), or in Ad19 only (335). Common effects: As shown previously for conjunctival epithelial cells, at 16h postinfection both serotypes increased host expression of nucleotide metabolism (RRM1, RRM2, TYMS), DNA replication licensing (MCMs 2-8 and CDT1) and cell cycle control (cyclins and CDC genes). Ad19 specific effects: these included decreases in the innate immune response genes IFIT2, ISG20, MX1 and CEACAM5 and increases in growth factors FGF2 and FGF13 and signaling molecules CXCL12 (SDF-1) and FZD7. Corneal vs. conjunctival effects: Of 279 panels modulated by Ad19 in 2 out of 3 independent experiments using conjunctival epithelial cells (previous data), 188 (67%) also were modulated by Ad19 in the present study.
As demonstrated for conjunctival epithelial cells, Ad5 and Ad19 share common mechanisms for subversion of host cell metabolism. Ad19 suppresses innate immune response more competently, and generates potent extracellular signals. Moreover, there is a substantial overlap of Ad19 effects between conjunctival and corneal cells.
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