Disparate Entry of Adenoviruses Dictates Differential Innate Immune Responses on the Ocular Surface

Pennington, Matthew R.; Saha, Amrita; Painter, David F.; Gavazzi, Christina; Ismail, Ashrafali M.; Zhou, Xiaohong; Chodosh, James; Rajaiya, Jaya

Human adenovirus infection of the ocular surface is associated with severe keratoconjunctivitis and the formation of subepithelial corneal infiltrates, which may persist and impair vision for months to years following infection. Long term pathology persists well beyond the resolution of viral replication, indicating that the prolonged immune response is not virus-mediated. However, it is not clear how these responses are sustained or even initiated following infection. This review discusses recent work from our laboratory and others which demonstrates different entry pathways specific to both adenovirus and cell type. These findings suggest that adenoviruses may stimulate specific pattern recognition receptors in an entry/trafficking-dependent manner, leading to distinct immune responses dependent on the virus/cell type combination. Additional work is needed to understand the specific connections between adenoviral entry and the stimulation of innate immune responses by the various cell types present on the ocular surface.