Spring viraemia of carp (SVC), caused by spring viraemia of carp virus (SVCV) is an important disease due to its drastic effects on carp fisheries in many countries. To better understand molecular responses to SVCV infection, two dimensional eletrophoresis (2-DE) and MALDI-TOF/TOF were performed to investigate altered proteins in epithelioma papulosum cyprini cells (EPCs). Differentially expressed proteins in mock-infected EPCs and SVCV-infected EPCs were compared. A total of 54 differentially expressed spots were successfully identified (33 up-regulated spots and 21 down-regulated spots) which include cytoskeleton proteins, macromolecular biosynthesis-associated proteins, stress response proteins, signal transduction proteins, energy metabolism, and ubiquitin proteasome pathway-associated proteins. Moreover, 7 corresponding genes of the differentially expressed proteins were quantified using real time RT-PCR to examine their transcriptional profiles. The presence of four selected cellular proteins (beta-actin, gamma1-actin, heat shock cognate 71 kDa protein and annexin A2) associated with the spring viraemia of carp virus (SVCV) particles was validated by Western blot assay. This study provides dynamic and useful protein-related information to further understand the underlying pathogenesis of SVCV infection. Proteomic analysis of epithelioma papulosum cyprini cells infected with spring viremia of carp virus. Fish Shellfish Immunol. 2013 Apr 10. pii: S1050-4648(13)00480-4. doi:10.1016/j.fsi.2013.03.367. Liyue Liu, Qin Li, Li Lin, Min Wang, Yuanan Lu, Weimin Wang, Junfa Yuan, Lijuan Li,Xueqin Liu. Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, W uhan 430 070, People ’s Republic of China.