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2019 OMIG Abstract

Sequence Variants of Adenovirus Type 8 Predict Pathogenicity

K. Nakamichi1, L. Akileswaran1, A. Lee1, C. Lee1, D. Stroman2, J. Rajaiya3, J. Chodosh3, R. Van Gelder1,4
Departments of 1Ophthalmology and 4Pathology and Biological Structure, University of Washington School of Medicine, Seattle, WA; 2 NovaBay, Emeryville, CA; 3 Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA

Adenoviral keratoconjunctivitis (AKC) remains a common and potentially debilitating ocular infection. While the predilection of certain adenoviral types, typically of the D species family, for causing conjunctivitis has been well described, other virus-specific pathogenicity factors have not been determined.

Methods: The BayNovation trial studied AKC in 500 subjects from four countries on three continents. Using Illumina NGS sequencing, we have analyzed the full viral genome from 80 adenovirus type 8 patient samples taken from the placebo arm of this trial and correlated sequence variants to outcomes. Full or nearly full genome reconstructions were obtained for 71 samples with an average sequence coverage of 330x.

Results: A total of 481 sequence variants from reference sequence were identified. Principle component analysis and other clustering methods identified three clear clades of viral sequence: one associated with strains from Sri Lanka, one in samples from India, and one shared by samples from India and Brazil. Likelihood of subepithelial infiltrates (SEI) was found to differ significantly between clades. Machine learning models suggest that approximately 76% of the likelihood of SEIs is attributable to viral sequence variants.

Conclusion: Adenoviral type 8 shows unexpected, geographically variant sequence heterogeneity. Sequence variants correspond with pathogenicity and may be useful in identifying patients at risk for poor outcomes from adenoviral keratoconjunctivitis, as well as identifying molecular mechanisms underlying pathogenicity.

Disclosure: N

Supported by NIH R21EY027453 (RVG), K23EY029246 (AL), K23EY024921 (CL), R01EY021558 (JR), R01EY013124 (JC), P30EY001730, an unrestricted grant from Research to Prevent Blindness, and the Mark J. Daily, MD Research Fund.


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