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S.A. Harvey, E.G. Romanowski, K.A. Yates, Y.J. Gordon; Transcriptomic Responses of Human Conjunctival Epithelial Cells to Adenovirus Serotype 19 Infection . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3047.
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© ARVO (1962-2015); The Authors (2016-present)
Adenovirus (Ad) is the major cause of viral conjunctivitis worldwide, with serotypes Ad8, Ad19 and Ad37 predominantly infecting the eye. We previously reported host cell transcriptomic (mRNA) responses to an ocular isolate of Ad5 (see IOVS 46, 3657–3665, 2005), and now explore the responses to Ad19.
Human conjunctival epithelial cells in primary culture were infected with Ad19 at multiplicities of infection (MOI) of 0, 0.1 or 1.0 and harvested at 1.5h, 6h or 16h post–infection. Total cell RNA was isolated, processed and analyzed using Affymetrix HU133 Plus 2.0 GeneChips (54,630 panels measuring host cell mRNAs). We focus here on changes of MOI=1.0 vs. MOI=0.0 at 16h postinfection.
Genes modulated by both Ad19 and Ad5: by increasing host expression ≥ 2 fold both serotypes took over host pathways for nucleotide metabolism (RRM2, TYMS, UNG), control of DNA replication (Pfs2, CDC6, MCM4, MCM6, MCM7), DNA recombination (RAD51, RAD51AP1) and direct (CCNE2, CDC25A, PRC1, ASK, GMNN) or indirect (USP1, LEF1) control of the cell cycle, plus 6 additional genes. Moreover, both serotypes decreased expression of the extracellular matrix (ECM) components COL1A1, COL1A2, COL3A1, and of cadherin CDH11. In contrast, 20 panels including 13 antiviral or interferon–induced (IFI) transcripts (CXCL10, CXCL11, IFIT1, IFIT3, IFI35, IFI44, IFI44L, IFIH1, OAS1, OASL, STAT1, GBP1, RSAD2) were increased ≥ 2 fold by Ad19 but decreased ≥ 1.5 fold by Ad5. Genes modulated by Ad19 and not by Ad5: combining the primary Ad19 data with an additional experiment using cells grown in secondary culture revealed 18 panels with consistent, time–dependent changes. Notably, Ad19 decreased PTGS2 (inducible cyclooxygenase for inflammatory prostanoid response) and MMP3 (ECM–degrading protease) at 6h. At 16h, Ad19–modulated panels were associated predominantly with differentiation/development: ENC1, WNT5A, ARID4A and 2 others decreased while PEG10, ZNF367, EID3, ELAVL2, RASEF, GPR54 and 5 others increased.
In contrast to the respiratory serotype Ad5, the preferential ocular tropism of Ad19 and subsequent productive infection likely depends both on its control of some host differentiation/development genes and on the different host defense /inflammatory responses it elicits.
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