Ocular infection of herpes simplex virus-1 (HSV1) can result in herpetic stromal keratitis (HSK), which impairs vision and is a common cause of human blindness.Studies indicated that HSK lesions are mainly orchestrated by CD4⁺ T cells.Herpesvirus entry mediator (HVEM), a tumor necrosis factor receptor superfamily member, facilitates virus entry through interactions with viral glycoprotein D (gD). HVEM, a widely expressed tumor necrosis factor (TNF) receptor superfamily member with diverse roles in immune signaling.Intriguingly, HVEM has five receptors: two costimulatory molecules (LIGHT and LT-α), two coinhibitory molecules (BTLA and CD160), and the HSV-gD.HVEM is referred to as a molecular switch because of its capacity to deliver costimulatory signals when bound to LIGHT/LT-α and to produce inhibitory signals when bound to BTLA/CD160.In this paper, the researching progress of the five receptors functions of HVEM and CD160/BTLA-HVEM-LIGHT/LT-α signaling pathway in the HSK were reviewed.We have to provide an insight into the pathogenesis of HSK and clinical ideas for the effective treatment of HSK.Through effective clinical intervention, the inflammatory immune response is reduced, thereby achieving therapeutic effects on recurrence of autoimmune diseases and chronic immune diseases.

Herpetic stromal keratitis; HVEM-BTLA/CD160; HVEM-LIGHT/LT-α; Signaling pathway; Pathogenesis mechanism