Rasgrp2 regulates the permissiveness of NIH3T3 cells to a herpes simplex virus 1 mutant with inactivated ICP34.5 gene

We have previously reported that mtHSV, a herpes simplex virus 1 (HSV-1) mutant with an inactivated gene for beta-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.