Adenovirus and the Cornea: More Than Meets the Eye

Abstract

Human adenoviruses cause disease at multiple mucosal sites, including the respiratory, gastrointestinal, and genitourinary tracts, and are common agents of conjunctivitis. One site of infection that has received sparse attention is the cornea, a transparent tissue and the window of the eye. While most adenovirus infections are self-limited, corneal inflammation (keratitis) due to adenovirus can persist or recur for months to years after infection, leading to reduced vision, discomfort, and light sensitivity. Topical corticosteroids effectively suppress late adenovirus keratitis but are associated with vision-threatening side effects. In this short review, we summarize current knowledge on infection of the cornea by adenoviruses, including corneal epithelial cell receptors and determinants of corneal tropism. We briefly discuss mechanisms of stromal keratitis due to adenovirus infection, and review an emerging therapy to mitigate adenovirus corneal infections based on evolving knowledge of corneal epithelial receptor usage.

The Epithelial Cell Glycocalyx in Ocular Surface Infection

“…An example is human adenoviruses (HAdV), one of the most common causes of ocular infection. Dozens of HAdVs, classified into seven species, A to G, have been identified on mucosal surfaces, but only a limited number of them cause epidemic keratoconjunctivitis in the eye ( 26 ). It appears that some of these viruses, primarily those belonging to species D, use sialic acid-containing glycans to establish infections at the ocular surface ( 27 ).…”

The Communication between Ocular Surface and Nasal Epithelia in 3D Cell Culture Technology for Translational Research: A Narrative Review

“…An effective treatment is lacking, and the mortality rate in immune-compromised patients can amount to up to 70% [ 134 ]. HAdV infections in the eye manifest as either follicular conjunctivitis, pharyngoconjunctival fever (PCF), or epidemic keratoconjunctivitis (EKC) involving the cornea (reviewed in [ 135 ]). EKC represents one of the most frequent ocular diseases and is mainly caused by species D adenoviruses including HAdV-8, HAdV-37, HAdV-53, HAdV-54, HAdV-56, HAdV-64 (previously known as HAdV-19a), HAdV-82, and HAdV-85 [ 135 ].…”

“…HAdV infections in the eye manifest as either follicular conjunctivitis, pharyngoconjunctival fever (PCF), or epidemic keratoconjunctivitis (EKC) involving the cornea (reviewed in [ 135 ]). EKC represents one of the most frequent ocular diseases and is mainly caused by species D adenoviruses including HAdV-8, HAdV-37, HAdV-53, HAdV-54, HAdV-56, HAdV-64 (previously known as HAdV-19a), HAdV-82, and HAdV-85 [ 135 ]. Among these, HAdV-8, HAdV-19, and HAdV-37 cause the most severe conjunctivitis [ 136 ].…”

“…Cell entry occurs by clathrin-mediated endocytosis [ 141 , 154 ]. This panel ( b ) was adapted from [ 135 ]. Abbreviations: Ad, adenovirus; MeV, wild-type, i.e., pathogenic measles virus; GD1a, ganglioside.…”

Special Issue “Adenovirus Pathogenesis”

“…The reviews update us on the molecular and cellular events taking place during more or less severe, persistent infections in eyes [6] and intestine [7]-and a case report describing the death of a neonate suffering from adenovirus-associated sepsis [8]-which remind us about the huge medical need for anti-adenovirus drugs. The Special Issue provides us with up-to-date knowledge about the intracellular functions of cellular RNAbinding zinc finger proteins [9], the DNA damage response [10], viral early proteins [10], and small non-coding RNA [11] during adenovirus replication, as well as the interactions between virions and extracellular proteins and how this contributes to the activation of mononuclear phagocytes [12].…”