The Role of Viral Pathogens in the Promotion of Epithelial–Mesenchymal Transition and Neoplastic Cell Invasion

Epithelial-to-mesenchymal transition (EMT) is a multistep process in which stationary, polarized epithelial cells lose cell-to-cell adhesion and acquire a mesenchymal phenotype with migratory and invasive properties. Migrating EMT cells express both epithelial and mesenchymal markers, an intermediate hybrid state that allows them to retain some epithelial traits for survival while gaining mobility. After migration and metastasis to a secondary tumor site, EMT cells revert to an epithelial-like state via a mesenchymal-to-epithelial transition (MET) to establish new tumors. Cells undergoing EMT may also acquire cancer stem cell properties, leading to chemotherapy resistance and cancer recurrence. Accumulating evidence suggests that both oncogenic and non-oncogenic viruses can induce EMT. Among the oncogenic viruses, EMT has been reported in neoplastic cells infected with human papillomavirus, hepatitis B and C viruses, Epstein–Barr virus, and Kaposi sarcoma-associated herpesvirus. Non-oncogenic viruses, including human cytomegalovirus and human immunodeficiency virus, can also induce EMT in neoplastic cells. Furthermore, coinfection of neoplastic cells with two or more oncogenic viruses or oncogenic and non-oncogenic viruses may lead to synergistic and/or additive effects with respect to EMT induction. This review presents our current understanding of the molecular mechanisms underlying virus-induced EMT and the role of this transition in promoting neoplastic disease.