title: Oncolytic bovine herpesvirus type 1 infects and kills breast tumor cells and breast cancer-initiating cells irrespective of tumor subtype.
abstract: Oncolytic viruses are attractive cancer therapeutics because of their unique mechanisms of tumor cell targeting and the absence of toxic side effects associated with current treatments. Bovine herpesvirus type 1 (BHV-1) is a species-specific herpesvirus that fails to induce cytopathic effects in normal human cells, but is capable of infecting and killing a variety of immortalized and transformed human cell types, including human breast tumor cell lines from luminal, basal A and basal B subtypes, representing a variety of receptor expression profiles. BHV-1 is capable of initiating replication in and killing both bulk and side population cells, the latter of which have enhanced tumor-initiating capacity. Despite the lack of a productive infection or secretion of cytotoxic factors, BHV-1 infection decreases cellular viability in long-term culture following low multiplicity of infection. Moreover, BHV-1-infected MCF7 cells are significantly diminished in their capacity to form tumors in vivo. Overall, these studies suggest that oncolytic BHV-1 targets bulk breast cancer cells and cancer-initiating cells from luminal and basal subtypes by a novel mechanism that is not contingent upon cellular receptor expression status.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
authors.forename: B P
authors.initials: BP
authors.lastname: Cuddington
authors.forename: A L
authors.initials: AL
authors.lastname: Dyer
authors.forename: S T
authors.initials: ST
authors.lastname: Workenhe
authors.forename: K L
authors.initials: KL
authors.lastname: Mossman
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy* / Q000821:virology*; D002417:Cattle; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D007242:Herpesvirus 1, Bovine / Q000502:physiology*; D006801:Humans; D061986:MCF-7 Cells; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000821:virology*; D050130:Oncolytic Virotherapy / Q000379:methods*; D015398:Signal Transduction; D014779:Virus Replication / Q000502:physiology