mTORC2-dependent autophagy inhibition regulates the replication of HSV-1 and adenovirus in viral keratitis & conjunctivitis.

Viral keratitis & conjunctivitis result in multiple ophthalmic symptoms and even progress to vision loss without timely intervention. Although multitudinous pathogens can cause ocular infections, the regulatory mechanisms underlying virus-host interactions remain incompletely defined. Our clinical and mechanistic investigations identify the co-infection of herpes simplex virus type 1 (HSV-1) and adenovirus as a predominant etiology of viral keratoconjunctivitis in Shenzhen, China (2024). The viral co-infection causes both severe symptoms and inflammations in clinical cases and in vitro. Mechanistically, mTORC2-regulated autophagy plays a pivotal role in viral replication, with mTOR-targeted intervention demonstrating superior antiviral and anti-inflammatory efficacy in corneal epithelial cells. This study elucidates a novel regulatory mechanism of mTORC2 in HSV-1 and adenovirus infection, thereby providing novel targets for the development of drugs against viral keratitis & conjunctivitis.