Bovine Herpesvirus VP22 Induces Apoptosis in Neuroblastoma Cells by Upregulating the Expression Ratio of Bax to Bcl-2

Abstract

Herpesvirus tegument protein VP22 has been shown to have biotherapeutic potential in tumor gene therapy. Some studies indicate that VP22 may enhance the transfer efficiency of therapeutic proteins by delivering them to more cells while trafficking. Our previous study showed that bovine herpesvirus VP22 (BVP22) enhanced equine herpesvirus thymidine kinase-ganciclovir (Etk-GCV) suicide gene therapy by an unknown intracellular effect. In this study, the interaction between BVP22 and host tumor cells was studied in neuroblastoma NXS2 cells. Cell cycle analysis was performed to determine whether BVP22 possesses biotherapeutic potential by altering the cell cycle, making cells more sensitive to therapeutic genes. As a result, the cell cycle was not affected by the transfection of BVP22 into NXS2 cells. However, cytotoxicity induced by BVP22 was observed in NXS2 cells on the second and third days after transient transfection. Further, analyses of caspase-3 activity and apoptosis suggested that BVP22 induces apoptosis in host tumor cells by upregulating the expression ratio of Bax to Bcl-2.

Porcine reproductive and respiratory syndrome virus induces apoptosis through a mitochondria-mediated pathway

“…Then tBid induces oligomerization of BAK and BAX, thereby inducing release of cytochrome c (Wei et al, 2001). Upregulation of Bax/Bcl-2 expression ratio is also a mechanism by which SARS coronavirus and Bovine herpesvirus (VP22 protein) induce mitochondria-mediated apoptosis (Qiu et al, 2005;Ren et al, 2005). Over-expression of Bcl-2 has been shown to inhibit the intrinsic apoptosis pathway mediated by mitochondria.…”

Alphaherpesvirus Major Tegument Protein VP22: Its Precise Function in the Viral Life Cycle

“…Disruption of ORF9p binding to AP-1 via point mutation of ORF9p severely impairs viral growth, most likely by preventing effective viral secondary envelopment ( Lebrun et al, 2018 ). MDV VP22 and HSV-2 VP22 also interact with AP-1 ( Qiu et al, 2005 ). In HSV-1 infected cells, VP22 may be activated via phosphorylation mediated by protein kinases encoded by the CKII and UL13 genes ( Elliott et al, 1996 ; Asai et al, 2007 ).…”

“…Apoptosis in the early stage of viral infection prevents replication of the virus, but apoptosis in the late stage of infection is beneficial for the release and spread of progeny virus ( Oral et al, 2016 ; Zhou et al, 2017 ). Transient expression of BoHV-1 VP22 in NXS2 cells does not affect the cell cycle, and analyses of caspase-3 activity and apoptosis have suggested that VP22 induces apoptosis in host tumor cells by upregulating the expression ratio of Bax to Bcl-2 ( Qiu et al, 2005 ). These results suggest that VP22 may promote the spread of viruses by stimulating apoptosis in the late stage of viral infection.…”

“…(Lebrun et al, 2018). MDV VP22 and HSV-2 VP22 also interact with AP-1 (Qiu et al, 2005). In HSV-1 infected cells, VP22 may be activated via phosphorylation mediated by protein kinases encoded by the CKII and UL13 genes (Elliott et al, 1996;Asai et al, 2007).…”