An emerging human eye disease is associated with aquatic virus zoonotic infection.

Climate change and human activities have increased the risk of virus spillover from wildlife, posing a threat to human health. A human ocular disease called persistent ocular hypertensive viral anterior uveitis (POH-VAU) has recently emerged; however, the cause is unclear. Here we report that POH-VAU is associated with covert mortality nodavirus (CMNV) of aquatic origin. CMNV is prevalent in farmed and wild aquatic animals worldwide. We confirmed CMNV infection in ocular tissues and seroconversion in 70 patients with POH-VAU. An exposure survey and analysis of logistic regression models revealed that CMNV exposure frequency, number of severe exposures and exposure severity were associated with an increased risk of POH-VAU. Epidemiological data indicate that frequent unprotected processing of aquatic animals and consumption of raw aquatic animals were commonly reported exposure events, collectively accounting for 71.4% of investigated cases. Challenge tests revealed that CMNV can cause elevated intraocular pressure and pathological damage to ocular tissues in mice and can infect mammalian cells in vitro. This study reveals that an aquatic animal virus is associated with an emerging human disease.