Human herpes simplex virus 1 (HSV-1) causes facial,ocular,and encephalitic disease and is associated with latent infection and cancer.Here,we developed a means of studying the pathogenesis of HSV-1 infection at the protein level by using the SELDI Protein Chip to detect changes of protein expression in Vero cells cultured in vitro.After infection with HSV-1 and culture for 12,24 or 48 h,cells were harvested and lysed.IMAC3 arrays were applied to SELDI-TOF-MS to detect proteomic differences before and after infection.The chip detected a series of differentially expressed protein peaks.Interestingly,both peaks at 16 912 Da and 17 581 Da corresponded precisely with the molecular mass of ISG 15,which may participate in antiviral activity during the process of infection.Thus,the results we obtained can serve as a basis to study the pathogenesis of HSV-1 and the interaction between the virus and its host.In addition,they can help in the discovery of new therapeutic targets for treatment of HSV-1 infection.