The ocular immune system and Flaviviruses: A crossroad between defense and disease

Flaviviruses are emerging arthropod-borne viruses that cause severe endemic infections and epidemics on a global scale. Recent Zika virus outbreaks have highlighted a significant link between the virus and ocular abnormalities, increasing interest in the pathogenesis of Flaviviruses. Flavivirus pathogenesis involves a complex interplay between viral replication and immune responses, leading to a wide spectrum of human diseases. Flavivirus infections can cause ocular complications that are usually self-limiting but can result in irreversible visual impairment and vision loss. These complications can affect both the anterior and posterior segments of the eye, and symptoms can range from mild conjunctivitis to more severe conditions like uveitis and even the inflammation of the optic nerve. Ocular inflammation often arises from the immune system's response to viral infections. In ocular Flavivirus infections, the immune response aims to protect the eye, but it can sometimes lead to inflammation and tissue damage. In this review, we summarize the current knowledge of the major Flaviviruses (Zika, Dengue, Yellow Fever, and West Nile) reported to cause ocular manifestations in humans, with emphasis on viral immunopathogenesis. Hence, we discuss how Flaviviruses modulate immune responses and cause ocular manifestations.