Influenza A Virus Utilizes the Nasolacrimal System to Establish Respiratory Infection after Ocular Exposure in the Swine Model.

Influenza A virus (IAV) can rapidly disseminate among animals through various transmission routes, with emerging evidence suggesting the ocular surface as an important entrance. However, it remains unclear how the virus invades the respiratory tract after ocular exposure. Here, we demonstrated that H1N1 (A/swine/Guangdong/1/2011) utilizes the nasolacrimal system to rapidly spread from the ocular surface to the respiratory tract in the porcine model. In vivo and ex vivo, IAV could efficiently attach and replicate in conjunctiva epithelium, which has abundance of α-2,6-linked and α-2,3-linked sialic acid. After ocular inoculation, infectious virions swiftly migrate to the nasolacrimal duct of piglets and, via continual drainage, disseminate to the respiratory tract. Moreover, the detection of continual virus shedding as well as the successful isolation of virus from conjunctiva and respiratory tract tissue indicated the establishment of productive infection after the transocular route. This study presents evidence suggesting that IAVs could utilize the nasolacrimal system to swiftly spread to the respiratory tract following ocular exposure, which contributes to understanding the modes of transocular transmission of IAVs.