title: Rasgrp2 regulates the permissiveness of NIH3T3 cells to a herpes simplex virus 1 mutant with inactivated ICP34.5 gene.
abstract: We have previously reported that mtHSV, a herpes simplex virus 1 (HSV-1) mutant with an inactivated gene for β-galactosidase, can efficiently lyse tumor but not normal cells. However, the mechanism of this selective oncolytic activity is so far unclear. In this study, using the phage display screening we identified the cellular protein binding to HSV-1 mutant (mtHSV) as (Ras guanyl releasing protein 2) Rasgrp2 which regulates the Ras signaling pathway. Rasgrp2 was found to bind directly to purified mtHSV as well as to mtHSV present within infected HeLa cells where it aggregated on the cell membrane. NIH3T3 cells were found nonpermissive to mtHSV but they became permissive following transformation with the Rasgrp2 gene. This effect was linked to the activation of the Ras-PKR signaling pathway. These observations indicate a key role of Rasgrp2 in the mtHSV infection of NIH3T3 cells and are important for the potential use of mtHSV in cancer therapy.
authors.affiliation: STate Key Laboratory of Virology, College of Life Science, Wuhan University, 430072, Wuhan, P.R. China.
authors.forename: W
authors.initials: W
authors.lastname: Xiao
authors.forename: Y
authors.initials: Y
authors.lastname: Su
authors.forename: S
authors.initials: S
authors.lastname: Zhou
authors.forename: Ch
authors.initials: Ch
authors.lastname: Yi
authors.forename: G
authors.initials: G
authors.lastname: He
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Qi
mesh_terms: D000818:Animals; D002470:Cell Survival; D005260:Female; D020868:Gene Silencing; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology*; D019151:Peptide Library; D015398:Signal Transduction; D013045:Species Specificity; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D053585:Virus Attachment; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D019151:Peptide Library; C415483:RASGRP2 protein, human; D014764:Viral Proteins; C066469:gamma 34.5 protein, Human herpesvirus 1; D001616:beta-Galactosidase