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.