title: Expression of the immediate early IE180 protein under the control of the hTERT and CEA tumor-specific promoters in recombinant pseudorabies viruses: Effects of IE180 protein on promoter activity and apoptosis induction.
abstract: Since the pseudorabies virus (PRV) genome encodes for a single immediate-early protein, IE180, we reasoned that this strong transactivating protein could represent a key regulatory switch that could be genetically manipulated in order to alter its tropism towards cancer cells. We therefore initiated studies to test whether the human telomerase reverse transcriptase (hTERT) and carcinoembryonic antigen (CEA) tumor promoters could functionally replace the IE180 promoter. We show that both promoters can functionally substitute the IE180 promoter in plasmid constructs and recombinant viruses, and observed that IE180 differentially auto-regulated each promoter tested, with PRV IE180 negatively regulating the hTERT promoter but positively hyper-activating the CEA promoter. Interestingly, we also observed that the recombinant PRV-TER and PRV-CEA viruses preferentially replicated in diverse cancer cell lines compared to control non-cancer cells, and the PRV-CEA was capable of additionally inducing a profound apoptotic phenotype which we correlated to the overexpression of IE180.
authors.affiliation: Departamento de Medicina Preventiva, Salud Pública y Microbiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid 28029, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Lerma
authors.affiliation: Departamento de Medicina Preventiva, Salud Pública y Microbiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid 28029, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Alcalá
authors.affiliation: Departamento de Medicina Preventiva, Salud Pública y Microbiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid 28029, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Piñero
authors.affiliation: Departamento de Medicina Preventiva, Salud Pública y Microbiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid 28029, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Torres
authors.affiliation: Departamento de Medicina Preventiva, Salud Pública y Microbiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid 28029, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Martin
authors.affiliation: Centro de Biología Molecular, CSIC-UAM, Cantoblanco, Madrid 28049, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Lim
authors.affiliation: Departamento de Medicina Preventiva, Salud Pública y Microbiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid 28029, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Sainz
authors.affiliation: Departamento de Medicina Preventiva, Salud Pública y Microbiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid 28029, Spain. Electronic address: enrique.tabares@uam.es.
authors.forename: E
authors.initials: E
authors.lastname: Tabarés
mesh_terms: D017209:Apoptosis; D002272:Carcinoembryonic Antigen / Q000235:genetics*; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D011558:Herpesvirus 1, Suid / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D011995:Recombination, Genetic; D019098:Telomerase / Q000235:genetics*; D014779:Virus Replication
chemical_list: C548518:CEA X protein, human; D002272:Carcinoembryonic Antigen; D017874:Immediate-Early Proteins; C509186:TERT protein, human; D019098:Telomerase
keywords: PRV IE180 activity hTERT CEA promoters