title: Herpes simplex virus-1 infection or Simian virus 40-mediated immortalization of corneal cells causes permanent translocation of NLRP3 to the nuclei.
abstract: OBJECTIVE
  To investigate into the potential involvement of pyrin containing 3 gene (NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.
  
  
  METHODS
  The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1 (HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40 (SV40)-immortalized human corneal epithelial cell line were also examined. Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.
  
  
  RESULTS
  The NLRP3 activation induced by HSV-1 infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore, in the SV40-immortalized human corneal epithelial cells, NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium (known as an inhibitor of NLRP3 activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.
  
  
  CONCLUSIONS
  It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.
authors.affiliation: Department of Immunology, Taishan Medical University, Tai'an 271016, Shandong Province, China ; Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Qingdao 266071, Shandong Province, China.
authors.forename: Shu-Long
authors.initials: SL
authors.lastname: Wang
authors.affiliation: Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Qingdao 266071, Shandong Province, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Qingdao 266071, Shandong Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Immunology, Qingdao University, Qingdao 266071, Shandong Province, China.
authors.forename: Xiao-Meng
authors.initials: XM
authors.lastname: Dong
authors.affiliation: Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Qingdao 266071, Shandong Province, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Immunology, Qingdao University, Qingdao 266071, Shandong Province, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Li
authors.affiliation: Department of Immunology, Taishan Medical University, Tai'an 271016, Shandong Province, China.
authors.forename: Wen-Gang
authors.initials: WG
authors.lastname: Song
authors.affiliation: Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Qingdao 266071, Shandong Province, China ; MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
authors.forename: Yi-Qiang
authors.initials: YQ
authors.lastname: Wang
keywords: Simian vacuolating virus 40; herpes simplex virus-1; human corneal epithelial cell; immortalization; inflammasome; keratitis; pyrin containing 3 gene; translocation