Molecular epidemiology of adenoviral pathogenesis in keratoconjunctivitis

University Of Washington, Seattle WA

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Abstract

Adenoviral conjunctivitis is one of the most common conditions in all of medicine. Despite being a common cause of morbidity world-wide, there are no known host or pathogen factors that predict clinical outcomes in adenoviral keratoconjunctivitis (AdV KC). A recent, large, international clinical study of adenovirus-related KC revealed that approximately 10% of patients suffer from sustained visual loss. Preliminary deep DNA sequencing of AdV has revealed an unexpected sequence diversity in the viral genome, with ~8% sequence divergence even amongst samples with the same hexon-defined molecular type. Remarkably, 20% of the patients in this study lacked any polymerase chain reaction (PCR) or deep DNA sequencing evidence for adenovirus. Given the unexpected molecular variation of adenovirus and a large spectrum of clinical outcome in KC, we propose to analyze host and viral factors contributing to poor outcome (Aim 1). Using next generation DNA sequencing, we propose to catalog the molecular variants of adenovirus and correlate these with clinical outcomes as well (Aim 2). The results of these studies will expand our understanding of the molecular pathogenesis of viral conjunctivitis, and may provide biomarkers for predicting outcomes from this condition. These advances will facilitate future efforts toward developing therapies for this common condition.