Comparative analysis of the tear protein profile in herpes simplex virus type 1 epithelial keratitis

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RESEARCH ARTICLE

Open Access

Comparative analysis of the tear protein profile in herpes simplex virus type 1 epithelial keratitis Hua Yang1,2,3,4,5, Xiaozhao Yang1,2,3,4,5*, Yani Wang1,2,3,4,5, Xuan Zheng1,2,3,4,5, Yi Zhang1,2,3,4,5 and Yan Shao1,2,3,4,5

Abstract Background: Herpes simplex virus type 1 (HSV-1) keratitis is a major cause of corneal blindness in the world, and an in-depth understanding of its pathogenesis may help improve existing diagnosis and treatment. The purpose of this study is to compare and analysis the total tear protein profile of HSV-1 epithelial keratitis patients, and to quantify the potential candidate biomarkers of HSV-1 epithelial keratitis. Methods: We investigated the proteome in tear fluid from three HSV-1 epithelial keratitis patients and three healthy control subjects using nano-scale liquid chromatography-tandem mass spectrometry (nLC-MS/MS) analysis. Functional annotation of differentially expressed proteins was done with the Gene Ontology (GO) analysis. ELISA was done to quantify the potential candidate biomarkers in 26 clinical cases. Results: Tear fluid from three HSV-1 epithelial keratitis patients and three healthy control subjects contained a total of 1275 proteins and 326 proteins were unique to tear fluid of HSV-1 epithelial keratitis patients. Bioinformatics analysis revealed that tear proteins from HSV-1 epithelial keratitis patients may be involved in metabolic processes, antigen presentation, inflammatory response, and in the TNF-mediated and T cell receptor pathways. Furthermore, IL1A, IL12B, DEFB4A, and CAMP, which are associated with the inflammatory response and inhibition of viral infection, were significantly more abundant in the HSV-1 epithelial keratitis patients than in the healthy control subjects. Conclusions: This study reports the proteomic profile of tears in HSV-1 epithelial keratitis for the first time and identifies a number of unique differentially expressed proteins. Keywords: HSV-1 epithelial keratitis, Tears, Proteome, Mass spectrometry, Bioinformation, ELISA

Background Herpes simplex virus type 1 (HSV-1) is the most important pathogen causing ocular diseases in the world [1]. More than 40,000 new cases caused by HSV-1 infection each year, which range from mild corneal epithelial inflammation to severe chronic corneal ulcerations [2, 3]. Despite the diagnosis and treatment of eye disease have * Correspondence: [email protected] 1 Department of Ophthalmology, Xi’an No.1 Hospital, Xi’an 710002, Shaanxi Province, China 2 Shaanxi Institute of Ophthalmology, Xi’an 710002, Shaanxi Province, China Full list of author information is available at the end of the article

enormous progress, HSV-1 keratitis still remains a leading cause of visual impairment and eventually blindness, and there is currently no effective vaccine available [4, 5]. Corneal disease due to HSV-1 commonly presents as epithelial keratitis which, though usually self-limiting, may persist or progress without treatment [2]. The use of antiviral drugs can effectively alleviate the