Bovine Herpesvirus 4 Induces Apoptosis of Human Carcinoma Cell Lines In vitro and In vivo

Abstract

The idea of using oncolytic viruses for the treatment of cancers was proposed a century ago. During the last two decades, viruses able to replicate specifically in cancer cells and to induce their lysis were identified and were genetically modified to improve their viro-oncolytic properties. More recently, a new approach consisting of inducing selective apoptosis in cancer cells through viral infection has been proposed; this approach has been called viro-oncoapoptosis. In the present study, we report the property of bovine herpesvirus-4 (BoHV-4) to induce, in vitro and in vivo, apoptosis of some human carcinomas. This conclusion relies on the following observations:

The Chemokine IL8 Is Up-Regulated in Bovine Endometrial Stromal Cells by the BoHV-4 IE2 Gene Product, ORF50/Rta: A Step Ahead Toward a Mechanism for BoHV-4 Induced Endometritis1

“…To determine whether BoHV-4 gene expression and replication is required for induction of IL8 in BESCs, BoHV-4 virions were treated with a psoralen compound and exposure to UV light. This treatment provokes DNA cross-linking in the viral genome without interfering with viral structural proteins [35], although total inhibition of BoHV-4 gene expression requires longer UV exposure to cause cross-linking throughout the entire viral genome [33]. Infection of BESCs with BoHV-4 treated with psoralen and UV light for 8 min prevented the induction of IL8 secretion (Fig.…”

“…Viral inactivation was performed as previously described [33]. Briefly, 2 3 10 6 viral plaque-forming units were incubated in 1 ml of MEM containing 5 lg/ml of psoralen (trioxsalen, 49-aminomethyl-HCl; Sigma) and incubated on ice in a 35-mm plastic Petri dish for various periods of time under ultraviolet (UV) light (302 nm, 0.12 A, UVM-57 lamp; Applietek) at a distance of 5 cm.…”

“…Briefly, 2 3 10 6 viral plaque-forming units were incubated in 1 ml of MEM containing 5 lg/ml of psoralen (trioxsalen, 49-aminomethyl-HCl; Sigma) and incubated on ice in a 35-mm plastic Petri dish for various periods of time under ultraviolet (UV) light (302 nm, 0.12 A, UVM-57 lamp; Applietek) at a distance of 5 cm. The efficiency of viral inactivation was monitored for each preparation by titration of residual infectivity on permissive MDBK cells [33]. …”

Recombinant Bovine Herpesvirus 4 (BoHV-4) Expressing Glycoprotein D of BoHV-1 Is Immunogenic and Elicits Serum-Neutralizing Antibodies against BoHV-1 in a Rabbit Model

“…Compared to other gammaherpesviruses, BoHV-4 contains few ho- mologs of cellular genes expected to alter the growth properties of cells (41). Although homologs of cellular genes carried by BOHV-4 have been shown to protect cells from apoptosis and BoHV-4 infection has been shown to inhibit apoptosis in some cell lines, in others, including some carcinoma cell lines, BoHV-4 infection triggers apoptosis instead (15).…”

Herpesvirus bovino 4 (BoHV-4): aspectos generales de su biología y situación en la República Argentina

“…En contraste con la mayoría de los gammaherpesvirus, el BoHV-4 presenta la capacidad de replicar en un amplio rango de especies 48 , entre las que se encuentran el bisonte americano, el búfalo africano, diferentes especies de ciervos, cabras, ovejas, especies no rumiantes como el león, el gato doméstico y el conejo 20,38,45,54,56,59,73 , y una gran variedad de cultivos celulares incluyendo líneas celulares y cultivos primarios de células de bovino, ovino, caprino, canino, felino, porcino, conejo y pollo, así como en varias líneas celulares de humano 26,39,49,58 .…”